Variant chr22-40404360-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000248929.14(SGSM3):c.271G>A(p.Asp91Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SGSM3
ENST00000248929.14 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.49

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:

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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=0.41897705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM3	NM_015705.6 linkuse as main transcript	c.271G>A	p.Asp91Asn	missense_variant	5/22	ENST00000248929.14	NP_056520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM3	ENST00000248929.14 linkuse as main transcript	c.271G>A	p.Asp91Asn	missense_variant	5/22	1	NM_015705.6	ENSP00000248929	P1	Q96HU1-1
SGSM3	ENST00000457767.5 linkuse as main transcript	c.70G>A	p.Asp24Asn	missense_variant	4/8	2		ENSP00000399249
SGSM3	ENST00000478085.5 linkuse as main transcript	n.248G>A		non_coding_transcript_exon_variant	1/9	2
SGSM3	ENST00000485962.5 linkuse as main transcript	n.432G>A		non_coding_transcript_exon_variant	5/20	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722876

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:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.271G>A (p.D91N) alteration is located in exon 5 (coding exon 4) of the SGSM3 gene. This alteration results from a G to A substitution at nucleotide position 271, causing the aspartic acid (D) at amino acid position 91 to be replaced by an asparagine (N). 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

Pathogenic

0.70

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

T;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.17

Sift

Benign

0.13

T;D

Sift4G

Benign

0.063

T;D

Polyphen

0.57

.;P

Vest4

0.90

MutPred

0.36

.;Gain of MoRF binding (P = 0.1054);

MVP

0.48

MPC

0.58

ClinPred

0.94

GERP RS

5.6

Varity_R

0.28

gMVP

0.56

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over