20-33439020-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003098.3(SNTA1):​c.317G>A​(p.Arg106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,613,974 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 10 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 16 hom. )

Consequence

SNTA1
NM_003098.3 missense

Scores

2
16

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.67
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.00801605).
BP6
Variant 20-33439020-C-T is Benign according to our data. Variant chr20-33439020-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 191576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-33439020-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00837 (1274/152256) while in subpopulation AFR AF= 0.0258 (1070/41548). AF 95% confidence interval is 0.0245. There are 10 homozygotes in gnomad4. There are 639 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1274 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNTA1NM_003098.3 linkc.317G>A p.Arg106Gln missense_variant 2/8 ENST00000217381.3 NP_003089.1 Q13424-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNTA1ENST00000217381.3 linkc.317G>A p.Arg106Gln missense_variant 2/81 NM_003098.3 ENSP00000217381.2 Q13424-1

Frequencies

GnomAD3 genomes
AF:
0.00839
AC:
1276
AN:
152138
Hom.:
11
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0259
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00347
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0103
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000470
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00291
AC:
732
AN:
251456
Hom.:
6
AF XY:
0.00241
AC XY:
328
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.0258
Gnomad AMR exome
AF:
0.00101
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00956
Gnomad NFE exome
AF:
0.000484
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00130
AC:
1904
AN:
1461718
Hom.:
16
Cov.:
32
AF XY:
0.00118
AC XY:
857
AN XY:
727170
show subpopulations
Gnomad4 AFR exome
AF:
0.0293
Gnomad4 AMR exome
AF:
0.00121
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00854
Gnomad4 NFE exome
AF:
0.000232
Gnomad4 OTH exome
AF:
0.00247
GnomAD4 genome
AF:
0.00837
AC:
1274
AN:
152256
Hom.:
10
Cov.:
33
AF XY:
0.00858
AC XY:
639
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0258
Gnomad4 AMR
AF:
0.00347
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0103
Gnomad4 NFE
AF:
0.000470
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00137
Hom.:
7
Bravo
AF:
0.00900
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.0234
AC:
103
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00322
AC:
391
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterresearchBiesecker Lab/Clinical Genomics Section, National Institutes of HealthJun 24, 2013- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
not provided Benign:3
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMar 20, 2018- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Long QT syndrome 12 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Long QT syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2025- -
Primary dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitterclinical testingCenter for Advanced Laboratory Medicine, UC San Diego Health, University of California San DiegoAug 21, 2017- -
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 10, 2015This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.67
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T
Eigen
Benign
-0.076
Eigen_PC
Benign
0.042
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.85
T
MetaRNN
Benign
0.0080
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.071
Sift
Benign
0.061
T
Sift4G
Benign
0.10
T
Polyphen
0.020
B
Vest4
0.28
MVP
0.35
MPC
0.38
ClinPred
0.012
T
GERP RS
4.0
Varity_R
0.16
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs75025585; hg19: chr20-32026826; API