9-128626364-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 ClinVar 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

GnomAD3 exomes AF: 0.795 AC: 196830 AN: 247550 Hom.: 81229 AF XY: 0.807 AC XY: 108249 AN XY: 134184

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 SAS exome AF: 0.777

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

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.784

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.778

Gnomad4 FIN exome AF: 0.828

Gnomad4 NFE exome AF: 0.899

Gnomad4 OTH exome AF: 0.824

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

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.766

Alfa AF: 0.811 Hom.: 10804

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

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. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

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