Variant 22-24847651-G-A 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_001098497.3(SGSM1):c.157G>A(p.Val53Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000584 in 1,613,492 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 1 hom. )

Consequence

SGSM1
NM_001098497.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

Variant links:

Genes affected

SGSM1 (HGNC:29410): (small G protein signaling modulator 1) Enables GTPase activator activity and small GTPase binding activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in cytoplasmic vesicle membrane and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SGSM1 links:

Genome browser will be placed here

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=0.05495572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM1	NM_001098497.3 link	c.157G>A	p.Val53Ile	missense_variant	4/25	ENST00000400358.9	NP_001091967.1	Q2NKQ1-4
SGSM1	NM_001039948.4 link	c.157G>A	p.Val53Ile	missense_variant	4/26		NP_001035037.1	Q2NKQ1-1
SGSM1	NM_133454.4 link	c.157G>A	p.Val53Ile	missense_variant	4/25		NP_597711.1	Q2NKQ1A0A087X241
SGSM1	NM_001098498.3 link	c.157G>A	p.Val53Ile	missense_variant	4/24		NP_001091968.1	Q2NKQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM1	ENST00000400358.9 link	c.157G>A	p.Val53Ile	missense_variant	4/25	1	NM_001098497.3	ENSP00000383211.4		Q2NKQ1-4

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000227

AC:

AN:

246266

Hom.:

AF XY:

0.000246

AC XY:

AN XY:

134204

show subpopulations

Gnomad AFR exome

AF:

0.0000679

Gnomad AMR exome

AF:

0.0000290

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:

0.000449

Gnomad OTH exome

AF:

0.000501

GnomAD4 exome

AF:

0.000615

AC:

899

AN:

1461322

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

440

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000760

Gnomad4 OTH exome

AF:

0.000796

GnomAD4 genome

AF:

0.000283

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000514

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000598

Hom.:

Bravo

AF:

0.000348

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000246

AC:

ESP6500EA

AF:

0.000485

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000237

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

Jul 17, 2024

The c.157G>A (p.V53I) alteration is located in exon 4 (coding exon 4) of the SGSM1 gene. This alteration results from a G to A substitution at nucleotide position 157, causing the valine (V) at amino acid position 53 to be replaced by an isoleucine (I). 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

0.063

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

.;.;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;M;M

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.040

.;N;N

REVEL

Benign

0.040

Sift

Benign

0.12

.;T;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.019, 0.018

.;B;B

Vest4

0.27

MVP

0.10

MPC

0.21

ClinPred

0.030

GERP RS

0.72

Varity_R

0.059

gMVP

0.19

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