Variant 22-40404267-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015705.6(SGSM3):c.178A>C(p.Ser60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,366,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SGSM3
NM_015705.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06297889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM3	NM_015705.6 linkuse as main transcript	c.178A>C	p.Ser60Arg	missense_variant	5/22	ENST00000248929.14	NP_056520.2	Q96HU1-1B9A6J5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SGSM3	ENST00000248929.14 linkuse as main transcript	c.178A>C	p.Ser60Arg	missense_variant	5/22	1	NM_015705.6	ENSP00000248929.8	Q96HU1-1
ENSG00000284431	ENST00000639722.1 linkuse as main transcript	n.*1416A>C		non_coding_transcript_exon_variant	16/31	5		ENSP00000492828.1	A0A1W2PRX2
ENSG00000284431	ENST00000639722.1 linkuse as main transcript	n.*1416A>C		3_prime_UTR_variant	16/31	5		ENSP00000492828.1	A0A1W2PRX2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000553

AC:

AN:

180826

Hom.:

AF XY:

0.00

AC XY:

AN XY:

95096

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000227

AC:

AN:

1366286

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

668986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000291

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.178A>C (p.S60R) alteration is located in exon 5 (coding exon 4) of the SGSM3 gene. This alteration results from a A to C substitution at nucleotide position 178, causing the serine (S) at amino acid position 60 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.51

DANN

Benign

0.47

DEOGEN2

Benign

0.040

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.26

M_CAP

Benign

0.0045

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.70

REVEL

Benign

0.035

Sift

Benign

0.27

Sift4G

Benign

0.50

Polyphen

0.0010

Vest4

0.18

MutPred

0.28

Loss of phosphorylation at S60 (P = 0.0258);

MVP

0.040

MPC

0.18

ClinPred

0.11

GERP RS

-9.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.046

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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