rs10760566

Variant names:

• chr9-128583939-A-C
• rs10760566
• NM_001130438.3:c.2163A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-128583939-A-C
• chr9-128583939-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001130438.3(SPTAN1):​c.2163A>C​(p.Ala721Ala) 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, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.800
• Publications: 21 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 -21 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 VariationId is 1166052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130438.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTAN1	NM_001130438.3	MANE Select	c.2163A>C	p.Ala721Ala	synonymous	Exon 16 of 57	NP_001123910.1
	SPTAN1	NM_001375318.1		c.2199A>C	p.Ala733Ala	synonymous	Exon 17 of 59	NP_001362247.1
	SPTAN1	NM_001375310.1		c.2163A>C	p.Ala721Ala	synonymous	Exon 16 of 58	NP_001362239.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTAN1	ENST00000372739.7	TSL:1 MANE Select	c.2163A>C	p.Ala721Ala	synonymous	Exon 16 of 57	ENSP00000361824.4
	SPTAN1	ENST00000372731.8	TSL:1	c.2163A>C	p.Ala721Ala	synonymous	Exon 16 of 56	ENSP00000361816.4
	SPTAN1	ENST00000358161.9	TSL:1	c.2163A>C	p.Ala721Ala	synonymous	Exon 16 of 55	ENSP00000350882.6

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

GnomAD2 exomes AF: 0.993 AC: 249498 AN: 251312 AF XY: 0.995

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 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

African (AFR) AF: 0.900 AC: 30146 AN: 33480

American (AMR) AF: 0.995 AC: 44478 AN: 44724

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26136 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39695 AN: 39700

South Asian (SAS) AF: 1.00 AC: 86238 AN: 86258

European-Finnish (FIN) AF: 1.00 AC: 53420 AN: 53420

Middle Eastern (MID) AF: 0.997 AC: 5752 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111812 AN: 1112008

Other (OTH) AF: 0.994 AC: 60020 AN: 60396

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

African (AFR) AF: 0.902 AC: 37440 AN: 41512

American (AMR) AF: 0.990 AC: 15139 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 0.999 AC: 4824 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68009 AN: 68036

Other (OTH) AF: 0.983 AC: 2077 AN: 2112

Alfa AF: 0.989 Hom.: 115282

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

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 100% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 93. Only high quality variants are reported.

Developmental and epileptic encephalopathy Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.5
DANN	Benign	0.58
PhyloP100		-0.80
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: rs10760566; hg19: chr9-131346218; COSMIC: COSV108182687; COSMIC: COSV108182687;