rs143730708

Variant names:

• chr22-40404396-C-G
• rs143730708
• NM_015705.6:c.307C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-40404396-C-G
• chr22-40404396-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SGSM3 NM_015705.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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]

ENSG00000284431 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3049379).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGSM3	NM_015705.6	c.307C>G	p.Arg103Gly	missense_variant	Exon 5 of 22	ENST00000248929.14	NP_056520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGSM3	ENST00000248929.14	c.307C>G	p.Arg103Gly	missense_variant	Exon 5 of 22	1	NM_015705.6	ENSP00000248929.8
ENSG00000284431	ENST00000639722.1	n.*1545C>G		non_coding_transcript_exon_variant	Exon 16 of 31	5		ENSP00000492828.1
ENSG00000284431	ENST00000639722.1	n.*1545C>G		3_prime_UTR_variant	Exon 16 of 31	5		ENSP00000492828.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 246000 Hom.: 0 AF XY: 0.00000753 AC XY: 1 AN XY: 132794

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 SAS 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.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.10
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.016	D;T
Polyphen		0.28	.;B
Vest4		0.26
MutPred		0.56		.;Gain of ubiquitination at K106 (P = 0.0393);
MVP		0.32
MPC		0.20
ClinPred		0.92	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.53

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

Other links and lift over

dbSNP: rs143730708; hg19: chr22-40800400;