Variant 22-40404617-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015705.6(SGSM3):c.427G>C(p.Glu143Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SGSM3
NM_015705.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.54

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 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=0.30406934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGSM3	NM_015705.6 link	c.427G>C	p.Glu143Gln	missense_variant	Exon 6 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.427G>C	p.Glu143Gln	missense_variant	Exon 6 of 22	1	NM_015705.6	ENSP00000248929.8	Q96HU1-1
ENSG00000284431	ENST00000639722.1 link	n.*1665G>C		non_coding_transcript_exon_variant	Exon 17 of 31	5		ENSP00000492828.1	A0A1W2PRX2
ENSG00000284431	ENST00000639722.1 link	n.*1665G>C		3_prime_UTR_variant	Exon 17 of 31	5		ENSP00000492828.1	A0A1W2PRX2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250488

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135438

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:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461378

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726980

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.427G>C (p.E143Q) alteration is located in exon 6 (coding exon 5) of the SGSM3 gene. This alteration results from a G to C substitution at nucleotide position 427, causing the glutamic acid (E) at amino acid position 143 to be replaced by a glutamine (Q). 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

0.30

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

T;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.15

Sift

Benign

0.14

T;T

Sift4G

Benign

0.064

T;T

Polyphen

0.057

.;B

Vest4

0.36

MutPred

0.54

.;Gain of MoRF binding (P = 0.0242);

MVP

0.25

MPC

0.26

ClinPred

0.46

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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