Variant 22-40404396-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000248929.14(SGSM3):c.307C>T(p.Arg103Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000407 in 1,608,836 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

SGSM3
ENST00000248929.14 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.63

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009180725).

BP6

Variant 22-40404396-C-T is Benign according to our data. Variant chr22-40404396-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 742761.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM3	NM_015705.6 linkuse as main transcript	c.307C>T	p.Arg103Cys	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.307C>T	p.Arg103Cys	missense_variant	5/22	1	NM_015705.6	ENSP00000248929	P1	Q96HU1-1
SGSM3	ENST00000457767.5 linkuse as main transcript	c.106C>T	p.Arg36Cys	missense_variant	4/8	2		ENSP00000399249
SGSM3	ENST00000478085.5 linkuse as main transcript	n.284C>T		non_coding_transcript_exon_variant	1/9	2
SGSM3	ENST00000485962.5 linkuse as main transcript	n.468C>T		non_coding_transcript_exon_variant	5/20	5

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00744

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000890

AC:

219

AN:

246000

Hom.:

AF XY:

0.000941

AC XY:

125

AN XY:

132794

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000471

Gnomad FIN exome

AF:

0.00775

Gnomad NFE exome

AF:

0.000252

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.000380

AC:

554

AN:

1456536

Hom.:

Cov.:

AF XY:

0.000373

AC XY:

270

AN XY:

724192

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000304

Gnomad4 FIN exome

AF:

0.00648

Gnomad4 NFE exome

AF:

0.000127

Gnomad4 OTH exome

AF:

0.000416

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152300

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00744

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000675

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.0092

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.30

.;B

Vest4

0.30

MVP

0.36

MPC

0.21

ClinPred

0.080

GERP RS

4.8

Varity_R

0.44

gMVP

0.54

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