rs551595039

chr9-128593053-TGA-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001130438.3(SPTAN1):c.3215+15_3215+16del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 1,607,102 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (1 hom.)
• Consequence: SPTAN1 NM_001130438.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.09

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 -12 ACMG points.

• BP6: Variant 9-128593053-TGA-T is Benign according to our data. Variant chr9-128593053-TGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 207278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 141 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTAN1	NM_001130438.3	c.3215+15_3215+16del		intron_variant		ENST00000372739.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTAN1	ENST00000372739.7	c.3215+15_3215+16del		intron_variant		1	NM_001130438.3	P3

Frequencies

GnomAD3 genomes AF: 0.000926 AC: 141 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000532 AC: 127 AN: 238540 Hom.: 1 AF XY: 0.000529 AC XY: 68 AN XY: 128540

Gnomad AFR exome AF: 0.00216

Gnomad AMR exome AF: 0.00143

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000345

Gnomad OTH exome AF: 0.00169

GnomAD4 exome AF: 0.000331 AC: 482 AN: 1454790 Hom.: 1 AF XY: 0.000340 AC XY: 246 AN XY: 722826

Gnomad4 AFR exome AF: 0.00177

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000354

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000300

Gnomad4 OTH exome AF: 0.000432

GnomAD4 genome AF: 0.000926 AC: 141 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000859 AC XY: 64 AN XY: 74476

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000651 Hom.: 0

Bravo AF: 0.00113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, flagged submission	clinical testing	GeneDx	Apr 22, 2014	The variant is found in EPILEPSY panel(s). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 11, 2014	The variant is found in EPILEPSY,INFANT-EPI panel(s). -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 07, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	Jan 06, 2020	- -

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Developmental and epileptic encephalopathy, 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs551595039; hg19: chr9-131355332;