1-202127996-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000367282.6(GPR37L1):c.886G>A(p.Glu296Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
GPR37L1
ENST00000367282.6 missense
ENST00000367282.6 missense
Scores
2
10
6
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
GPR37L1 (HGNC:14923): (G protein-coupled receptor 37 like 1) Enables G protein-coupled peptide receptor activity; peptide binding activity; and prosaposin receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and positive regulation of MAPK cascade. Located in plasma membrane. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GPR37L1 | NM_004767.5 | c.886G>A | p.Glu296Lys | missense_variant | 2/2 | ENST00000367282.6 | NP_004758.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GPR37L1 | ENST00000367282.6 | c.886G>A | p.Glu296Lys | missense_variant | 2/2 | 1 | NM_004767.5 | ENSP00000356251 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152092Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000108 AC: 27AN: 250648Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135460
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GnomAD4 exome AF: 0.000109 AC: 160AN: 1461854Hom.: 0 Cov.: 34 AF XY: 0.000103 AC XY: 75AN XY: 727234
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74294
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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 | Sep 07, 2022 | The c.886G>A (p.E296K) alteration is located in exon 2 (coding exon 2) of the GPR37L1 gene. This alteration results from a G to A substitution at nucleotide position 886, causing the glutamic acid (E) at amino acid position 296 to be replaced by a lysine (K). 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
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
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