dbSNP rs61741902: SGSM2:p.Val1041Ile (chr17-2379485-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

14 publications found

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-AS1 (HGNC:56091): (SGSM2 antisense RNA 1)

SGSM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SGSM2	NM_014853.3 link	c.3121G>A	p.Val1041Ile	missense_variant	Exon 24 of 24	ENST00000268989.8	NP_055668.2	O43147-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGSM2	ENST00000268989.8 link	c.3121G>A	p.Val1041Ile	missense_variant	Exon 24 of 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

GnomAD2 exomes

AF:

0.0102

AC:

2567

AN:

250844

AF XY:

0.0102

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 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

African (AFR)

AF:

0.00188

AC:

AN:

33476

American (AMR)

AF:

0.00615

AC:

275

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

341

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0103

AC:

892

AN:

86234

European-Finnish (FIN)

AF:

0.0141

AC:

749

AN:

53148

Middle Eastern (MID)

AF:

0.00573

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0134

AC:

14872

AN:

1111724

Other (OTH)

AF:

0.00949

AC:

573

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

997

1994

2992

3989

4986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

562

1124

1686

2248

2810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00901

AC:

1372

AN:

152310

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

633

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00265

AC:

110

AN:

41560

American (AMR)

AF:

0.00803

AC:

123

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00704

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0117

AC:

124

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0131

AC:

894

AN:

68020

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

136

204

272

340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0112

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

(source)

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

PhyloP100

8.1

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

PromoterAI

0.052

Neutral

(source)

Varity_R

0.18

gMVP

0.38

Mutation Taster

=63/37

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over