chr1-108897045-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_013296.5(GPSM2):c.238A>G(p.Lys80Glu) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GPSM2
NM_013296.5 missense
NM_013296.5 missense
Scores
4
10
4
Clinical Significance
Conservation
PhyloP100: 9.32
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.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPSM2 | NM_013296.5 | c.238A>G | p.Lys80Glu | missense_variant | 3/15 | ENST00000264126.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPSM2 | ENST00000264126.9 | c.238A>G | p.Lys80Glu | missense_variant | 3/15 | 1 | NM_013296.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 152258Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460120Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726498
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74394
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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 | GeneDx | Oct 24, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T;.;.;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.;D;.;D;.
REVEL
Uncertain
Sift
Benign
D;.;T;.;D;.
Sift4G
Uncertain
D;.;T;.;D;.
Polyphen
B;.;.;B;B;.
Vest4
MutPred
Loss of ubiquitination at K80 (P = 0.0192);Loss of ubiquitination at K80 (P = 0.0192);Loss of ubiquitination at K80 (P = 0.0192);Loss of ubiquitination at K80 (P = 0.0192);Loss of ubiquitination at K80 (P = 0.0192);Loss of ubiquitination at K80 (P = 0.0192);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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