Variant chr12-122716231-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006018.3(HCAR3):c.507C>G(p.Ile169Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

HCAR3
NM_006018.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.351

Variant links:

Genes affected

HCAR3 (HGNC:16824): (hydroxycarboxylic acid receptor 3) Predicted to enable GTP binding activity and purinergic nucleotide receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]

HCAR3 links:

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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=0.09964928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCAR3	NM_006018.3 linkuse as main transcript	c.507C>G	p.Ile169Met	missense_variant	1/1	ENST00000528880.3	NP_006009.2	P49019

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCAR3	ENST00000528880.3 linkuse as main transcript	c.507C>G	p.Ile169Met	missense_variant	1/1	6	NM_006018.3	ENSP00000436714.2		P49019

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251466

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00000958

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Oct 27, 2022

The c.507C>G (p.I169M) alteration is located in exon 1 (coding exon 1) of the HCAR3 gene. This alteration results from a C to G substitution at nucleotide position 507, causing the isoleucine (I) at amino acid position 169 to be replaced by a methionine (M). 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

0.097

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.2

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.33

M_CAP

Benign

0.015

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.30

PROVEAN

Benign

0.14

REVEL

Benign

0.17

Sift

Benign

0.21

Sift4G

Benign

0.26

Vest4

0.045

MutPred

0.51

Loss of ubiquitination at K166 (P = 0.1351);

MVP

0.35

MPC

1.1

ClinPred

0.069

GERP RS

-1.2

Varity_R

0.10

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over