Variant 2-1083588-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018968.4(SNTG2):c.143C>T(p.Thr48Met) variant causes a missense change. The variant allele was found at a frequency of 0.000763 in 1,613,644 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00057 ( 2 hom. )

Consequence

SNTG2
NM_018968.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.71

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0102390945).

BP6

Variant 2-1083588-C-T is Benign according to our data. Variant chr2-1083588-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 724559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTG2	NM_018968.4 linkuse as main transcript	c.143C>T	p.Thr48Met	missense_variant	2/17	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.143C>T	p.Thr48Met	missense_variant	2/17	1	NM_018968.4	ENSP00000311837	P1	Q9NY99-1
SNTG2	ENST00000407292.1 linkuse as main transcript	c.143C>T	p.Thr48Met	missense_variant	2/11	1		ENSP00000385020		Q9NY99-2
SNTG2	ENST00000450962.5 linkuse as main transcript	c.143C>T	p.Thr48Met	missense_variant, NMD_transcript_variant	2/8	5		ENSP00000401997
SNTG2	ENST00000452177.5 linkuse as main transcript	c.143C>T	p.Thr48Met	missense_variant, NMD_transcript_variant	2/8	2		ENSP00000412249

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

399

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00903

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000779

AC:

194

AN:

249060

Hom.:

AF XY:

0.000548

AC XY:

AN XY:

135096

show subpopulations

Gnomad AFR exome

AF:

0.00969

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000569

AC:

832

AN:

1461450

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

389

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.00983

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000387

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.00263

AC:

400

AN:

152194

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00903

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00275

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00573

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.000843

AC:

102

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.27

MVP

0.50

MPC

0.15

ClinPred

0.046

GERP RS

4.2

Varity_R

0.49

gMVP

0.63

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

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