rs116747979

Variant names:

• chr20-33408776-G-A
• rs116747979
• NM_003098.3:c.1350C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-33408776-G-A
• chr20-33408776-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001424414.1(SNTA1):​c.1382C>T​(p.Ser461Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,614,120 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S461S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.011 (34 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (25 hom.)
• Consequence: SNTA1 NM_001424414.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.856
• Publications: 3 publications found

Genes affected

SNTA1 (HGNC:11167): (syntrophin alpha 1) Syntrophins are cytoplasmic peripheral membrane scaffold proteins that are components of the dystrophin-associated protein complex. This gene is a member of the syntrophin gene family and encodes the most common syntrophin isoform found in cardiac tissues. The N-terminal PDZ domain of this syntrophin protein interacts with the C-terminus of the pore-forming alpha subunit (SCN5A) of the cardiac sodium channel Nav1.5. This protein also associates cardiac sodium channels with the nitric oxide synthase-PMCA4b (plasma membrane Ca-ATPase subtype 4b) complex in cardiomyocytes. This gene is a susceptibility locus for Long-QT syndrome (LQT) - an inherited disorder associated with sudden cardiac death from arrhythmia - and sudden infant death syndrome (SIDS). This protein also associates with dystrophin and dystrophin-related proteins at the neuromuscular junction and alters intracellular calcium ion levels in muscle tissue. [provided by RefSeq, Jan 2013]

SNTA1 Gene-Disease associations (from GenCC):

• long QT syndrome 12

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000288878 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 20-33408776-G-A is Benign according to our data. Variant chr20-33408776-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 239498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0112 (1703/152268) while in subpopulation AFR AF = 0.0385 (1601/41550). AF 95% confidence interval is 0.037. There are 34 homozygotes in GnomAd4. There are 784 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1703 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424414.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTA1	NM_003098.3	MANE Select	c.1350C>T	p.Phe450Phe	synonymous	Exon 7 of 8	NP_003089.1	Q13424-1
	SNTA1	NM_001424414.1		c.1382C>T	p.Ser461Leu	missense	Exon 7 of 8	NP_001411343.1
	SNTA1	NM_001424413.1		c.1350C>T	p.Phe450Phe	synonymous	Exon 7 of 8	NP_001411342.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTA1	ENST00000217381.3	TSL:1 MANE Select	c.1350C>T	p.Phe450Phe	synonymous	Exon 7 of 8	ENSP00000217381.2	Q13424-1
	SNTA1	ENST00000953206.1		c.1382C>T	p.Ser461Leu	missense	Exon 7 of 8	ENSP00000623265.1
	SNTA1	ENST00000953198.1		c.1382C>T	p.Ser461Leu	missense	Exon 7 of 8	ENSP00000623257.1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1702 AN: 152150 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00288 AC: 724 AN: 251430 AF XY: 0.00213

Gnomad AFR exome AF: 0.0386

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00198

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00112 AC: 1637 AN: 1461852 Hom.: 25 Cov.: 31 AF XY: 0.00100 AC XY: 729 AN XY: 727226

African (AFR) AF: 0.0385 AC: 1290 AN: 33480

American (AMR) AF: 0.00179 AC: 80 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 48 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111980

Other (OTH) AF: 0.00240 AC: 145 AN: 60394

GnomAD4 genome AF: 0.0112 AC: 1703 AN: 152268 Hom.: 34 Cov.: 32 AF XY: 0.0105 AC XY: 784 AN XY: 74460

African (AFR) AF: 0.0385 AC: 1601 AN: 41550

American (AMR) AF: 0.00386 AC: 59 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68022

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00590 Hom.: 7

Bravo AF: 0.0121

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Long QT syndrome 12 (2)
-	-	2	not provided (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.1
DANN	Benign	0.68
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism

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: rs116747979; hg19: chr20-31996582; COSMIC: COSV104581719;