3-170084471-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014373.3(GPR160):​c.499C>A​(p.Gln167Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

GPR160
NM_014373.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.944
Variant links:
Genes affected
GPR160 (HGNC:23693): (G protein-coupled receptor 160) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. 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 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=0.059562236).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR160NM_014373.3 linkc.499C>A p.Gln167Lys missense_variant Exon 4 of 4 ENST00000355897.10 NP_055188.1 Q9UJ42

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPR160ENST00000355897.10 linkc.499C>A p.Gln167Lys missense_variant Exon 4 of 4 1 NM_014373.3 ENSP00000348161.5 Q9UJ42
GPR160ENST00000485735.6 linkc.*10C>A downstream_gene_variant 2 ENSP00000419546.2 C9JTZ7
GPR160ENST00000473675.1 linkc.*68C>A downstream_gene_variant 3 ENSP00000420751.1 C9JBW1
GPR160ENST00000482710.1 linkc.*234C>A downstream_gene_variant 2 ENSP00000419400.1 C9JUZ9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250704
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135478
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461386
Hom.:
0
Cov.:
30
AF XY:
0.0000110
AC XY:
8
AN XY:
727002
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000189

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.499C>A (p.Q167K) alteration is located in exon 4 (coding exon 1) of the GPR160 gene. This alteration results from a C to A substitution at nucleotide position 499, causing the glutamine (Q) at amino acid position 167 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
11
DANN
Benign
0.48
DEOGEN2
Benign
0.029
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.060
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
M
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.12
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.023
B
Vest4
0.14
MutPred
0.23
Gain of ubiquitination at Q167 (P = 0.0276);
MVP
0.030
MPC
0.18
ClinPred
0.035
T
GERP RS
3.1
Varity_R
0.055
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1034414232; hg19: chr3-169802259; API