Variant chr22-40401643-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000248929.14(SGSM3):c.58T>C(p.Trp20Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00961 in 1,613,356 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0066 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0099 ( 98 hom. )

Consequence

SGSM3
ENST00000248929.14 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.45

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005639255).

BP6

Variant 22-40401643-T-C is Benign according to our data. Variant chr22-40401643-T-C is described in ClinVar as [Benign]. Clinvar id is 782757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM3	NM_015705.6 linkuse as main transcript	c.58T>C	p.Trp20Arg	missense_variant	3/22	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.58T>C	p.Trp20Arg	missense_variant	3/22	1	NM_015705.6	ENSP00000248929	P1	Q96HU1-1
SGSM3	ENST00000457767.5 linkuse as main transcript	c.-111-496T>C		intron_variant		2		ENSP00000399249
SGSM3	ENST00000485962.5 linkuse as main transcript	n.219T>C		non_coding_transcript_exon_variant	3/20	5

Frequencies

GnomAD3 genomes

AF:

0.00656

AC:

998

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00586

AC:

1473

AN:

251474

Hom.:

AF XY:

0.00600

AC XY:

815

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00343

Gnomad FIN exome

AF:

0.00323

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00993

AC:

14506

AN:

1461022

Hom.:

Cov.:

AF XY:

0.00977

AC XY:

7099

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00264

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00359

Gnomad4 FIN exome

AF:

0.00392

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.00955

GnomAD4 genome

AF:

0.00655

AC:

998

AN:

152334

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

411

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00914

Hom.:

Bravo

AF:

0.00620

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.00565

AC:

686

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0101

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	Feb 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0056

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.20

Sift

Uncertain

0.011

Sift4G

Benign

0.17

Polyphen

0.94

Vest4

0.48

MutPred

0.46

Gain of disorder (P = 5e-04);

MVP

0.34

MPC

0.74

ClinPred

0.047

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: -50

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