22-40401643-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015705.6(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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0066 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0099 ( 98 hom. )

Consequence

SGSM3
NM_015705.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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:

ENSG00000284431 (HGNC:):

ENSG00000284431 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SGSM3	NM_015705.6 link	c.58T>C	p.Trp20Arg	missense_variant	Exon 3 of 22	ENST00000248929.14	NP_056520.2	Q96HU1-1B9A6J5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SGSM3	ENST00000248929.14 link	c.58T>C	p.Trp20Arg	missense_variant	Exon 3 of 22	1	NM_015705.6	ENSP00000248929.8	Q96HU1-1
ENSG00000284431	ENST00000639722.1 link	n.*1296T>C		non_coding_transcript_exon_variant	Exon 14 of 31	5		ENSP00000492828.1	A0A1W2PRX2
ENSG00000284431	ENST00000639722.1 link	n.*1296T>C		3_prime_UTR_variant	Exon 14 of 31	5		ENSP00000492828.1	A0A1W2PRX2

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

GnomAD2 exomes

AF:

0.00586

AC:

1473

AN:

251474

AF XY:

0.00600

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 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

AC:

AN:

33458

Gnomad4 AMR exome

AF:

0.00264

AC:

118

AN:

44702

Gnomad4 ASJ exome

AF:

0.00176

AC:

AN:

26102

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39654

Gnomad4 SAS exome

AF:

0.00359

AC:

310

AN:

86248

Gnomad4 FIN exome

AF:

0.00392

AC:

209

AN:

53360

Gnomad4 NFE exome

AF:

0.0119

AC:

13177

AN:

1111422

Gnomad4 Remaining exome

AF:

0.00955

AC:

576

AN:

60322

Heterozygous variant carriers

690

1379

2069

2758

3448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.00218939

AN:

0.00218939

Gnomad4 AMR

AF:

0.00288

AC:

0.00287544

AN:

0.00287544

Gnomad4 ASJ

AF:

0.00202

AC:

0.00201613

AN:

0.00201613

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00394

AC:

0.00393538

AN:

0.00393538

Gnomad4 FIN

AF:

0.00254

AC:

0.00254094

AN:

0.00254094

Gnomad4 NFE

AF:

0.0117

AC:

0.0116696

AN:

0.0116696

Gnomad4 OTH

AF:

0.00664

AC:

0.00663507

AN:

0.00663507

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00898

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SGSM3: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 07, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

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

Mutation Taster

=50/50

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