chr1-108885572-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_013296.5(GPSM2):c.50G>A(p.Arg17His) variant causes a missense change. The variant allele was found at a frequency of 0.000021 in 1,573,634 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
GPSM2
NM_013296.5 missense
NM_013296.5 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 5.29
Genes affected
GPSM2 (HGNC:29501): (G protein signaling modulator 2) The protein encoded by this gene belongs to a family of proteins that modulate activation of G proteins, which transduce extracellular signals received by cell surface receptors into integrated cellular responses. The N-terminal half of this protein contains 10 copies of leu-gly-asn (LGN) repeat, and the C-terminal half contains 4 GoLoco motifs, which are involved in guanine nucleotide exchange. This protein may play a role in neuroblast division and in the development of normal hearing. Mutations in this gene are associated with autosomal recessive nonsyndromic deafness (DFNB82). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]
CLCC1 (HGNC:29675): (chloride channel CLIC like 1) Predicted to enable chloride channel activity. Predicted to be involved in chloride transport. Located in endoplasmic reticulum and mitochondria-associated endoplasmic reticulum membrane. Implicated in retinitis pigmentosa 32. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.25875667).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPSM2 | NM_013296.5 | c.50G>A | p.Arg17His | missense_variant | 2/15 | ENST00000264126.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPSM2 | ENST00000264126.9 | c.50G>A | p.Arg17His | missense_variant | 2/15 | 1 | NM_013296.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249742Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135204
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GnomAD4 exome AF: 0.0000218 AC: 31AN: 1421526Hom.: 0 Cov.: 24 AF XY: 0.0000211 AC XY: 15AN XY: 709738
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 18, 2021 | This sequence change replaces arginine with histidine at codon 17 of the GPSM2 protein (p.Arg17His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs773654932, ExAC 0.003%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with GPSM2-related conditions. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;.;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;N;N;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;.;N;.;N;N
REVEL
Benign
Sift
Benign
D;.;T;.;D;.;T;T
Sift4G
Benign
T;.;T;.;T;.;T;T
Polyphen
B;.;.;B;B;.;.;.
Vest4
MutPred
Loss of methylation at R17 (P = 0.0262);Loss of methylation at R17 (P = 0.0262);Loss of methylation at R17 (P = 0.0262);Loss of methylation at R17 (P = 0.0262);Loss of methylation at R17 (P = 0.0262);Loss of methylation at R17 (P = 0.0262);Loss of methylation at R17 (P = 0.0262);Loss of methylation at R17 (P = 0.0262);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at