10-25395938-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020752.3(GPR158):c.1036G>A(p.Val346Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000474 in 1,603,962 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 0 hom. )
Consequence
GPR158
NM_020752.3 missense
NM_020752.3 missense
Scores
5
8
Clinical Significance
Conservation
PhyloP100: 6.80
Genes affected
GPR158 (HGNC:23689): (G protein-coupled receptor 158) Predicted to enable G protein-coupled receptor activity. Predicted to act upstream of or within G protein-coupled receptor signaling pathway and protein localization to plasma membrane. Predicted to be located in membrane. [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=0.22049528).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPR158 | NM_020752.3 | c.1036G>A | p.Val346Ile | missense_variant | 3/11 | ENST00000376351.4 | |
GPR158 | XR_930512.4 | n.1456G>A | non_coding_transcript_exon_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPR158 | ENST00000376351.4 | c.1036G>A | p.Val346Ile | missense_variant | 3/11 | 1 | NM_020752.3 | P2 | |
GPR158 | ENST00000650135.1 | c.799G>A | p.Val267Ile | missense_variant | 4/12 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152100Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251042Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135714
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GnomAD4 exome AF: 0.0000482 AC: 70AN: 1451862Hom.: 0 Cov.: 27 AF XY: 0.0000512 AC XY: 37AN XY: 722928
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74292
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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 | Jul 19, 2022 | The c.1036G>A (p.V346I) alteration is located in exon 3 (coding exon 3) of the GPR158 gene. This alteration results from a G to A substitution at nucleotide position 1036, causing the valine (V) at amino acid position 346 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
0.98
.;D
Vest4
0.58
MVP
0.068
MPC
0.22
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at