rs61741902

chr17-2379485-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.12

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007389635).
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGSM2	NM_014853.3	c.3121G>A	p.Val1041Ile	missense_variant	24/24	ENST00000268989.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGSM2	ENST00000268989.8	c.3121G>A	p.Val1041Ile	missense_variant	24/24	1	NM_014853.3	P4

Frequencies

GnomAD3 genomes AF: 0.00901 AC: 1372 AN: 152192 Hom.: 9 Cov.: 33

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.: 15 AF XY: 0.0102 AC XY: 1389 AN XY: 135720

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.: 32 AF XY: 0.0122 AC XY: 8857 AN XY: 726854

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.: 9 Cov.: 33 AF XY: 0.00850 AC XY: 633 AN XY: 74472

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.: 14

Bravo AF: 0.00827

TwinsUK AF: 0.0159 AC: 59

ALSPAC AF: 0.0148 AC: 57

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0138 AC: 119

ExAC AF: 0.00988 AC: 1199

Asia WGS AF: 0.00606 AC: 21 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	T
BayesDel_noAF	Benign	-0.50
Cadd	Uncertain	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
MetaRNN	Benign	0.0074	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
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	T
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

Other links and lift over

dbSNP: rs61741902; hg19: chr17-2282779; COSMIC: COSV51512833; COSMIC: COSV51512833;