Variant chr22-40404316-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000248929.14(SGSM3):c.227G>A(p.Arg76Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000469 in 1,578,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

SGSM3
ENST00000248929.14 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

Variant links:

Genes affected

SGSM3 (HGNC:25228): (small G protein signaling modulator 3) Enables GTPase activator activity and small GTPase binding activity. Involved in several processes, including Rap protein signal transduction; positive regulation of GTPase activity; and regulation of Rab protein signal transduction. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SGSM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043554604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM3	NM_015705.6 linkuse as main transcript	c.227G>A	p.Arg76Gln	missense_variant	5/22	ENST00000248929.14	NP_056520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM3	ENST00000248929.14 linkuse as main transcript	c.227G>A	p.Arg76Gln	missense_variant	5/22	1	NM_015705.6	ENSP00000248929	P1	Q96HU1-1
SGSM3	ENST00000457767.5 linkuse as main transcript	c.26G>A	p.Arg9Gln	missense_variant	4/8	2		ENSP00000399249
SGSM3	ENST00000478085.5 linkuse as main transcript	n.204G>A		non_coding_transcript_exon_variant	1/9	2
SGSM3	ENST00000485962.5 linkuse as main transcript	n.388G>A		non_coding_transcript_exon_variant	5/20	5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000185

AC:

AN:

222192

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

118888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000806

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000561

Gnomad SAS exome

AF:

0.0000822

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000398

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000477

AC:

AN:

1426578

Hom.:

Cov.:

AF XY:

0.0000566

AC XY:

AN XY:

706152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000731

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.0000748

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000165

Gnomad4 OTH exome

AF:

0.000102

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 14, 2022

The c.227G>A (p.R76Q) alteration is located in exon 5 (coding exon 4) of the SGSM3 gene. This alteration results from a G to A substitution at nucleotide position 227, causing the arginine (R) at amino acid position 76 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.012

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

.;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.60

N;N

REVEL

Benign

0.056

Sift

Benign

0.70

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.026

.;B

Vest4

0.27

MutPred

0.48

.;Gain of loop (P = 0.069);

MVP

0.22

MPC

0.18

ClinPred

0.027

GERP RS

4.4

Varity_R

0.026

gMVP

0.51

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