rs10760566

chr9-128583939-A-Cchr9-128583939-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001130438.3(SPTAN1):c.2163A>C(p.Ala721=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,614,148 control chromosomes in the GnomAD database, including 798,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (72052 hom., cov: 32)
  • Exomes 𝑓: 1.0 (726927 hom.)
• Consequence: SPTAN1 NM_001130438.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.800

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 9-128583939-A-C is Benign according to our data. Variant chr9-128583939-A-C is described in ClinVar as [Benign]. Clinvar id is 1166052.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128583939-A-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTAN1	NM_001130438.3	c.2163A>C	p.Ala721=	synonymous_variant	16/57	ENST00000372739.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTAN1	ENST00000372739.7	c.2163A>C	p.Ala721=	synonymous_variant	16/57	1	NM_001130438.3	P3

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147867 AN: 152140 Hom.: 72010 Cov.: 32

Gnomad AFR AF: 0.902

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.983

GnomAD3 exomes AF: 0.993 AC: 249498 AN: 251312 Hom.: 123920 AF XY: 0.995 AC XY: 135081 AN XY: 135804

Gnomad AFR exome AF: 0.903

Gnomad AMR exome AF: 0.995

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.997 AC: 1457697 AN: 1461890 Hom.: 726927 Cov.: 76 AF XY: 0.998 AC XY: 725463 AN XY: 727246

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 0.995

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.994

GnomAD4 genome AF: 0.972 AC: 147966 AN: 152258 Hom.: 72052 Cov.: 32 AF XY: 0.973 AC XY: 72427 AN XY: 74462

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.990

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.983

Alfa AF: 0.992 Hom.: 85667

Bravo AF: 0.968

Asia WGS AF: 0.997 AC: 3467 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	8.5
Dann	Benign	0.58

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: rs10760566; hg19: chr9-131346218;