Variant 8-50502836-G-C 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_018967.5(SNTG1):c.422G>C(p.Arg141Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000307 in 1,613,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

SNTG1
NM_018967.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.94

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:

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=0.14853075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNTG1	NM_018967.5 linkuse as main transcript	c.422G>C	p.Arg141Thr	missense_variant	9/19	ENST00000642720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNTG1	ENST00000642720.2 linkuse as main transcript	c.422G>C	p.Arg141Thr	missense_variant	9/19		NM_018967.5	P1	Q9NSN8-1

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000227

AC:

AN:

251060

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000485

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000311

AC:

454

AN:

1461194

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

230

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000397

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000270

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000410

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000492

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.422G>C (p.R141T) alteration is located in exon 9 (coding exon 7) of the SNTG1 gene. This alteration results from a G to C substitution at nucleotide position 422, causing the arginine (R) at amino acid position 141 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Oct 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.023

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

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

.;.;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.0039

MetaRNN

Benign

0.15

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;.;.;L;.;.;L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.1

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

REVEL

Benign

0.16

Sift

Benign

0.41

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

Sift4G

Benign

0.26

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

Polyphen

0.28

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

Vest4

0.55

MVP

0.61

MPC

0.086

ClinPred

0.069

GERP RS

4.9

Varity_R

0.33

gMVP

0.35

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