Variant 17-2361739-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014853.3(SGSM2):c.236G>C(p.Cys79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,613,804 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 31 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 20 hom. )

Consequence

SGSM2
NM_014853.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0460

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038831532).

BP6

Variant 17-2361739-G-C is Benign according to our data. Variant chr17-2361739-G-C is described in ClinVar as [Benign]. Clinvar id is 785548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1598/152344) while in subpopulation AFR AF= 0.0355 (1476/41580). AF 95% confidence interval is 0.034. There are 31 homozygotes in gnomad4. There are 734 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM2	NM_014853.3 linkuse as main transcript	c.236G>C	p.Cys79Ser	missense_variant	3/24	ENST00000268989.8	NP_055668.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM2	ENST00000268989.8 linkuse as main transcript	c.236G>C	p.Cys79Ser	missense_variant	3/24	1	NM_014853.3	ENSP00000268989	P4	O43147-2

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1596

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0356

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

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:

0.000191

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00279

AC:

699

AN:

250686

Hom.:

AF XY:

0.00212

AC XY:

287

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00102

AC:

1493

AN:

1461460

Hom.:

Cov.:

AF XY:

0.000858

AC XY:

624

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.0337

Gnomad4 AMR exome

AF:

0.00282

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000737

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.0105

AC:

1598

AN:

152344

Hom.:

Cov.:

AF XY:

0.00985

AC XY:

734

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0355

Gnomad4 AMR

AF:

0.00568

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.0119

ESP6500AA

AF:

0.0331

AC:

146

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00341

AC:

414

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 28, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.13

.;T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.72

T;T;T

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.8

N;N;.

REVEL

Benign

0.15

Sift

Benign

0.25

T;T;.

Sift4G

Benign

0.52

T;T;T

Polyphen

0.066

B;B;B

Vest4

0.60

MutPred

0.67

Loss of helix (P = 0.0123);Loss of helix (P = 0.0123);Loss of helix (P = 0.0123);

MVP

0.25

MPC

0.16

ClinPred

0.0042

GERP RS

3.2

Varity_R

0.050

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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