chr17-2375864-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014853.3(SGSM2):ā€‹c.2473G>Cā€‹(p.Ala825Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000525 in 1,523,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000015 ( 0 hom. )

Consequence

SGSM2
NM_014853.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.22
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-AS1 (HGNC:56091): (SGSM2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18036401).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SGSM2NM_014853.3 linkuse as main transcriptc.2473G>C p.Ala825Pro missense_variant 18/24 ENST00000268989.8 NP_055668.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SGSM2ENST00000268989.8 linkuse as main transcriptc.2473G>C p.Ala825Pro missense_variant 18/241 NM_014853.3 ENSP00000268989 P4O43147-2
SGSM2ENST00000426855.6 linkuse as main transcriptc.2338G>C p.Ala780Pro missense_variant 17/231 ENSP00000415107 A1O43147-1
SGSM2-AS1ENST00000574290.1 linkuse as main transcriptn.402-172C>G intron_variant, non_coding_transcript_variant 5
SGSM2ENST00000574563.5 linkuse as main transcriptc.2338G>C p.Ala780Pro missense_variant 17/232 ENSP00000459126 O43147-5

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
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
GnomAD3 exomes
AF:
0.0000279
AC:
5
AN:
179082
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
94958
show subpopulations
Gnomad AFR exome
AF:
0.000328
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000146
AC:
2
AN:
1371132
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
674104
show subpopulations
Gnomad4 AFR exome
AF:
0.0000646
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
AF:
0.0000394
AC:
6
AN:
152330
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000507
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsMay 20, 2024The c.2473G>C (p.A825P) alteration is located in exon 18 (coding exon 18) of the SGSM2 gene. This alteration results from a G to C substitution at nucleotide position 2473, causing the alanine (A) at amino acid position 825 to be replaced by a proline (P). 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
0.19
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.033
.;T;.
Eigen
Benign
-0.074
Eigen_PC
Benign
0.091
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.4
.;L;L
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.88
N;N;.
REVEL
Benign
0.12
Sift
Benign
0.15
T;T;.
Sift4G
Benign
0.13
T;T;T
Polyphen
0.0
B;D;B
Vest4
0.65
MutPred
0.50
.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP
0.34
MPC
0.18
ClinPred
0.13
T
GERP RS
5.3
Varity_R
0.29
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs547116331; hg19: chr17-2279158; API