NM_001130438.3:c.6280-27C>T

Variant names:

• chr9-128626364-C-T
• rs3737308
• NM_001130438.3:c.6280-27C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001130438.3(SPTAN1):​c.6280-27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 1,611,742 control chromosomes in the GnomAD database, including 590,112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (43339 hom., cov: 32)
  • Exomes 𝑓: 0.86 (546773 hom.)
• Consequence: SPTAN1 NM_001130438.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.617
• Publications: 11 publications found

Genes affected

SPTAN1 (HGNC:11273): (spectrin alpha, non-erythrocytic 1) Spectrins are a family of filamentous cytoskeletal proteins that function as essential scaffold proteins that stabilize the plasma membrane and organize intracellular organelles. Spectrins are composed of alpha and beta dimers that associate to form tetramers linked in a head-to-head arrangement. This gene encodes an alpha spectrin that is specifically expressed in nonerythrocytic cells. The encoded protein has been implicated in other cellular functions including DNA repair and cell cycle regulation. Mutations in this gene are the cause of early infantile epileptic encephalopathy-5. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010]

SPTAN1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-128626364-C-T is Benign according to our data. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626364-C-T is described in CliVar as Benign. Clinvar id is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTAN1	NM_001130438.3	c.6280-27C>T		intron_variant	Intron 48 of 56	ENST00000372739.7	NP_001123910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTAN1	ENST00000372739.7	c.6280-27C>T		intron_variant	Intron 48 of 56	1	NM_001130438.3	ENSP00000361824.4

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109285 AN: 152030 Hom.: 43327 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.767

GnomAD2 exomes AF: 0.795 AC: 196830 AN: 247550 AF XY: 0.807

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.892

Gnomad EAS exome AF: 0.520

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.897

Gnomad OTH exome AF: 0.831

GnomAD4 exome AF: 0.859 AC: 1253250 AN: 1459594 Hom.: 546773 Cov.: 52 AF XY: 0.858 AC XY: 623315 AN XY: 726168

African (AFR) AF: 0.349 AC: 11668 AN: 33446

American (AMR) AF: 0.784 AC: 35043 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 23260 AN: 26136

East Asian (EAS) AF: 0.502 AC: 19942 AN: 39696

South Asian (SAS) AF: 0.778 AC: 67033 AN: 86186

European-Finnish (FIN) AF: 0.828 AC: 43154 AN: 52110

Middle Eastern (MID) AF: 0.817 AC: 4205 AN: 5150

European-Non Finnish (NFE) AF: 0.899 AC: 999232 AN: 1111854

Other (OTH) AF: 0.824 AC: 49713 AN: 60298

GnomAD4 genome AF: 0.718 AC: 109317 AN: 152148 Hom.: 43339 Cov.: 32 AF XY: 0.716 AC XY: 53229 AN XY: 74364

African (AFR) AF: 0.370 AC: 15362 AN: 41502

American (AMR) AF: 0.782 AC: 11961 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3103 AN: 3472

East Asian (EAS) AF: 0.530 AC: 2725 AN: 5146

South Asian (SAS) AF: 0.753 AC: 3636 AN: 4830

European-Finnish (FIN) AF: 0.817 AC: 8654 AN: 10586

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61142 AN: 67996

Other (OTH) AF: 0.766 AC: 1620 AN: 2114

Alfa AF: 0.822 Hom.: 18488

Bravo AF: 0.700

Asia WGS AF: 0.625 AC: 2174 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 90. Only high quality variants are reported. -

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Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.59
PhyloP100		-0.62
PromoterAI		0.045	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3737308; hg19: chr9-131388643; COSMIC: COSV63986963; COSMIC: COSV63986963;