Genetic Variant NM_003098.3:c.200C>A (chr20-33443421-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003098.3(SNTA1):c.200C>A(p.Ala67Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A67V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNTA1
NM_003098.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.155

Publications

0 publications found

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]

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

SNTA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10256311).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003098.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNTA1	NM_003098.3	MANE Select	c.200C>A	p.Ala67Asp	missense	Exon 1 of 8	NP_003089.1	Q13424-1
SNTA1	NM_001424413.1		c.200C>A	p.Ala67Asp	missense	Exon 1 of 8	NP_001411342.1
SNTA1	NM_001424414.1		c.200C>A	p.Ala67Asp	missense	Exon 1 of 8	NP_001411343.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNTA1	ENST00000217381.3	TSL:1 MANE Select	c.200C>A	p.Ala67Asp	missense	Exon 1 of 8	ENSP00000217381.2	Q13424-1
SNTA1	ENST00000953204.1		c.200C>A	p.Ala67Asp	missense	Exon 1 of 9	ENSP00000623263.1
SNTA1	ENST00000953205.1		c.200C>A	p.Ala67Asp	missense	Exon 1 of 9	ENSP00000623264.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1180502

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

575678

African (AFR)

AF:

0.00

AC:

AN:

23070

American (AMR)

AF:

0.00

AC:

AN:

9476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15992

East Asian (EAS)

AF:

0.00

AC:

AN:

25964

South Asian (SAS)

AF:

0.00

AC:

AN:

46770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3214

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

981004

Other (OTH)

AF:

0.00

AC:

AN:

47734

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.17

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.51

M_CAP

Benign

0.049

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.66

PhyloP100

0.15

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.14

REVEL

Benign

0.036

Sift

Benign

0.33

Sift4G

Benign

0.70

Polyphen

0.43

Vest4

0.083

MutPred

0.17

Loss of glycosylation at P70 (P = 0.322)

MVP

0.55

MPC

0.41

ClinPred

0.13

GERP RS

3.6

PromoterAI

0.015

Neutral

(source)

Varity_R

0.23

gMVP

0.31

Mutation Taster

=70/30

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over