14-52598275-A-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001099652.2(GPR137C):c.448A>T(p.Ile150Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000426 in 1,339,092 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 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
GPR137C
NM_001099652.2 missense
NM_001099652.2 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 5.67
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05739695).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPR137C | NM_001099652.2 | c.448A>T | p.Ile150Leu | missense_variant | 2/7 | ENST00000321662.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPR137C | ENST00000321662.11 | c.448A>T | p.Ile150Leu | missense_variant | 2/7 | 1 | NM_001099652.2 | P1 | |
GPR137C | ENST00000542169.6 | c.310A>T | p.Ile104Leu | missense_variant | 2/8 | 1 | |||
GPR137C | ENST00000555622.1 | c.244A>T | p.Ile82Leu | missense_variant | 3/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000841 AC: 11AN: 130736Hom.: 0 AF XY: 0.000101 AC XY: 7AN XY: 69246
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GnomAD4 exome AF: 0.0000404 AC: 48AN: 1186900Hom.: 0 Cov.: 16 AF XY: 0.0000439 AC XY: 26AN XY: 592182
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74346
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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 | Jun 28, 2023 | The c.448A>T (p.I150L) alteration is located in exon 2 (coding exon 2) of the GPR137C gene. This alteration results from a A to T substitution at nucleotide position 448, causing the isoleucine (I) at amino acid position 150 to be replaced by a leucine (L). 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
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of ubiquitination at K152 (P = 0.115);
MVP
MPC
ClinPred
T
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