Variant 22-40404614-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001350048.2(SGSM3):c.-122C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,613,562 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: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

SGSM3
NM_001350048.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

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=0.3925264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGSM3	NM_015705.6 link	c.424C>T	p.Arg142Cys	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.424C>T	p.Arg142Cys	missense_variant	Exon 6 of 22	1	NM_015705.6	ENSP00000248929.8	Q96HU1-1
ENSG00000284431	ENST00000639722.1 link	n.*1662C>T		non_coding_transcript_exon_variant	Exon 17 of 31	5		ENSP00000492828.1	A0A1W2PRX2
ENSG00000284431	ENST00000639722.1 link	n.*1662C>T		3_prime_UTR_variant	Exon 17 of 31	5		ENSP00000492828.1	A0A1W2PRX2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

250570

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000318

AC:

465

AN:

1461420

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

237

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000405

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000164

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000269

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.424C>T (p.R142C) alteration is located in exon 6 (coding exon 5) of the SGSM3 gene. This alteration results from a C to T substitution at nucleotide position 424, causing the arginine (R) at amino acid position 142 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.019

D;D

Sift4G

Uncertain

0.032

D;D

Polyphen

1.0

.;D

Vest4

0.76

MVP

0.36

MPC

0.67

ClinPred

0.87

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.65

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

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