Variant chr17-2379485-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014853.3(SGSM2):c.3121G>A(p.Val1041Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,613,586 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0090 ( 9 hom., cov: 33)

Exomes 𝑓: 0.012 ( 118 hom. )

Consequence

SGSM2
NM_014853.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.12

Variant links:

Genes affected

SGSM2 (HGNC:29026): (small G protein signaling modulator 2) The protein encoded by this gene is a GTPase activator with activity towards RAB32 and RAB33B, which are regulators of membrane trafficking. The encoded protein inactivates RAB32 and can bind RAB9A-GTP, a protein required for RAB32 activation. [provided by RefSeq, Oct 2016]

SGSM2 links:

SGSM2 (HGNC:):

SGSM2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007389635).

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM2	NM_014853.3 linkuse as main transcript	c.3121G>A	p.Val1041Ile	missense_variant	24/24	ENST00000268989.8	NP_055668.2	O43147-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM2	ENST00000268989.8 linkuse as main transcript	c.3121G>A	p.Val1041Ile	missense_variant	24/24	1	NM_014853.3	ENSP00000268989.3		O43147-2

Frequencies

GnomAD3 genomes

AF:

0.00901

AC:

1372

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00804

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.0102

AC:

2567

AN:

250844

Hom.:

AF XY:

0.0102

AC XY:

1389

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.00216

Gnomad AMR exome

AF:

0.00619

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00991

Gnomad FIN exome

AF:

0.0154

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0122

AC:

17798

AN:

1461276

Hom.:

118

Cov.:

AF XY:

0.0122

AC XY:

8857

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00615

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.00949

GnomAD4 genome

AF:

0.00901

AC:

1372

AN:

152310

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

633

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.00803

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.0117

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.00827

TwinsUK

AF:

0.0159

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0138

AC:

119

ExAC

AF:

0.00988

AC:

1199

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.28

Sift

Benign

0.054

T;D

Sift4G

Uncertain

0.053

T;T

Polyphen

0.34

B;P

Vest4

0.25

MPC

0.13

ClinPred

0.024

GERP RS

5.3

Varity_R

0.18

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over