Genetic Variant NM_014853.3:c.2311G>C (chr17-2375702-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014853.3(SGSM2):c.2311G>C(p.Gly771Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,174 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 0.000026 ( 0 hom., cov: 32)

Consequence

SGSM2
NM_014853.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.73

Publications

0 publications found

Variant links:

Genes affected

SGSM2 (HGNC:29026): (small G protein signaling modulator 2) The protein encoded by this gene is a GTPase activator with activity towards RAB32 and RAB33B, which are regulators of membrane trafficking. The encoded protein inactivates RAB32 and can bind RAB9A-GTP, a protein required for RAB32 activation. [provided by RefSeq, Oct 2016]

SGSM2 links:

SGSM2-AS1 (HGNC:56091): (SGSM2 antisense RNA 1)

SGSM2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31601223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014853.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGSM2	NM_014853.3	MANE Select	c.2311G>C	p.Gly771Arg	missense	Exon 18 of 24	NP_055668.2	O43147-2
SGSM2	NM_001098509.2		c.2176G>C	p.Gly726Arg	missense	Exon 17 of 23	NP_001091979.1	O43147-1
SGSM2	NM_001346700.2		c.2176G>C	p.Gly726Arg	missense	Exon 17 of 23	NP_001333629.1	O43147-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGSM2	ENST00000268989.8	TSL:1 MANE Select	c.2311G>C	p.Gly771Arg	missense	Exon 18 of 24	ENSP00000268989.3	O43147-2
SGSM2	ENST00000426855.6	TSL:1	c.2176G>C	p.Gly726Arg	missense	Exon 17 of 23	ENSP00000415107.2	O43147-1
SGSM2	ENST00000968832.1		c.2314G>C	p.Gly772Arg	missense	Exon 18 of 24	ENSP00000638891.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250678

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.047

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.029

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

7.7

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.0

REVEL

Benign

0.13

Sift

Uncertain

0.022

Sift4G

Benign

0.10

Polyphen

0.63

Vest4

0.72

MutPred

0.24

Gain of solvent accessibility (P = 0.019)

MVP

0.45

MPC

0.26

ClinPred

0.58

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.43

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over