Variant chr8-50449698-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018967.5(SNTG1):c.250G>A(p.Val84Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,594,966 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 19 hom. )

Consequence

SNTG1
NM_018967.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0430

Variant links:

Genes affected

SNTG1 (HGNC:13740): (syntrophin gamma 1) The protein encoded by this gene is a member of the syntrophin family. Syntrophins are cytoplasmic peripheral membrane proteins that typically contain 2 pleckstrin homology (PH) domains, a PDZ domain that bisects the first PH domain, and a C-terminal domain that mediates dystrophin binding. This family member plays a role in mediating gamma-enolase trafficking to the plasma membrane and in enhancing its neurotrophic activity. Mutations in this gene are associated with idiopathic scoliosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

SNTG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008958966).

BP6

Variant 8-50449698-G-A is Benign according to our data. Variant chr8-50449698-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050595.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTG1	NM_018967.5 link	c.250G>A	p.Val84Ile	missense_variant	Exon 6 of 19	ENST00000642720.2	NP_061840.1	Q9NSN8-1A0A024R7Y0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTG1	ENST00000642720.2 link	c.250G>A	p.Val84Ile	missense_variant	Exon 6 of 19		NM_018967.5	ENSP00000493900.1		Q9NSN8-1

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

207

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00136

AC:

335

AN:

245820

Hom.:

AF XY:

0.00151

AC XY:

201

AN XY:

133012

show subpopulations

Gnomad AFR exome

AF:

0.000378

Gnomad AMR exome

AF:

0.000941

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00219

Gnomad OTH exome

AF:

0.00203

GnomAD4 exome

AF:

0.00238

AC:

3429

AN:

1442786

Hom.:

Cov.:

AF XY:

0.00237

AC XY:

1704

AN XY:

717518

show subpopulations

Gnomad4 AFR exome

AF:

0.000303

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.000133

Gnomad4 NFE exome

AF:

0.00284

Gnomad4 OTH exome

AF:

0.00198

GnomAD4 genome

AF:

0.00135

AC:

206

AN:

152180

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00226

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00207

Hom.:

Bravo

AF:

0.00146

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00137

AC:

166

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SNTG1-related disorder

Benign:1

Nov 10, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.4

DANN

Benign

0.38

DEOGEN2

Benign

0.021

T;T;.;.;.;T;.;.;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.82

.;.;T;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0090

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.79

N;N;.;.;.;N;.;N;.;.;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

0.60

N;.;.;.;.;N;.;N;.;N;.;.

REVEL

Benign

0.11

Sift

Benign

1.0

T;.;.;.;.;T;.;T;.;T;.;.

Sift4G

Benign

1.0

T;.;.;.;.;T;.;T;.;T;.;.

Polyphen

0.0

B;B;.;.;.;B;.;B;.;.;.;.

Vest4

0.22

MVP

0.26

MPC

0.046

ClinPred

0.0012

GERP RS

-4.6

Varity_R

0.019

gMVP

0.11

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