Variant 2-1098202-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018968.4(SNTG2):c.217A>G(p.Thr73Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000229 in 1,614,032 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

SNTG2
NM_018968.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57

Variant links:

Genes affected

SNTG2 (HGNC:13741): (syntrophin gamma 2) This gene encodes a protein belonging to the syntrophin family. Syntrophins are cytoplasmic peripheral membrane proteins that bind to components of mechanosenstive sodium channels and the extreme carboxy-terminal domain of dystrophin and dystrophin-related proteins. The PDZ domain of this protein product interacts with a protein component of a mechanosensitive sodium channel that affects channel gating. Absence or reduction of this protein product has been associated with Duchenne muscular dystrophy. There is evidence of alternative splicing yet the full-length nature of these variants has not been described. [provided by RefSeq, Jul 2008]

SNTG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10106847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTG2	NM_018968.4 linkuse as main transcript	c.217A>G	p.Thr73Ala	missense_variant	3/17	ENST00000308624.10	NP_061841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTG2	ENST00000308624.10 linkuse as main transcript	c.217A>G	p.Thr73Ala	missense_variant	3/17	1	NM_018968.4	ENSP00000311837	P1	Q9NY99-1
SNTG2	ENST00000407292.1 linkuse as main transcript	c.210+14547A>G		intron_variant		1		ENSP00000385020		Q9NY99-2
SNTG2	ENST00000450962.5 linkuse as main transcript	c.217A>G	p.Thr73Ala	missense_variant, NMD_transcript_variant	3/8	5		ENSP00000401997
SNTG2	ENST00000452177.5 linkuse as main transcript	c.217A>G	p.Thr73Ala	missense_variant, NMD_transcript_variant	3/8	2		ENSP00000412249

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000249

AC:

AN:

249242

Hom.:

AF XY:

0.000311

AC XY:

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.000581

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000239

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000204

AC:

298

AN:

1461690

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

167

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.000473

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000388

Hom.:

Bravo

AF:

0.000559

ESP6500AA

AF:

0.00109

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000290

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.217A>G (p.T73A) alteration is located in exon 3 (coding exon 3) of the SNTG2 gene. This alteration results from a A to G substitution at nucleotide position 217, causing the threonine (T) at amino acid position 73 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.60

M_CAP

Benign

0.034

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.29

Sift

Benign

0.067

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.59

MVP

0.48

MPC

0.45

ClinPred

0.045

GERP RS

4.7

Varity_R

0.26

gMVP

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over