dbSNP rs143730708: SGSM3:p.Arg103Gly (chr22-40404396-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015705.6(SGSM3):c.307C>G(p.Arg103Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R103C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

SGSM3
NM_015705.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.63

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: G2P

SGSM3 links:

ENSG00000284431 (HGNC:):

ENSG00000284431 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3049379).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015705.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SGSM3	NM_015705.6	MANE Select	c.307C>G	p.Arg103Gly	missense	Exon 5 of 22	NP_056520.2
SGSM3	NM_001350039.2		c.307C>G	p.Arg103Gly	missense	Exon 5 of 22	NP_001336968.1
SGSM3	NM_001350040.2		c.307C>G	p.Arg103Gly	missense	Exon 5 of 22	NP_001336969.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGSM3	ENST00000248929.14	TSL:1 MANE Select	c.307C>G	p.Arg103Gly	missense	Exon 5 of 22	ENSP00000248929.8	Q96HU1-1
ENSG00000284431	ENST00000639722.1	TSL:5	n.*1545C>G		non_coding_transcript_exon	Exon 16 of 31	ENSP00000492828.1	A0A1W2PRX2
ENSG00000284431	ENST00000639722.1	TSL:5	n.*1545C>G		3_prime_UTR	Exon 16 of 31	ENSP00000492828.1	A0A1W2PRX2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

246000

AF XY:

0.00000753

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.014

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

4.6

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.10

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.016

Polyphen

0.28

Vest4

0.26

MutPred

0.56

Gain of ubiquitination at K106 (P = 0.0393)

MVP

0.32

MPC

0.20

ClinPred

0.92

GERP RS

4.8

Varity_R

0.38

gMVP

0.53

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over