Variant 12-122715986-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006018.3(HCAR3):c.752G>A(p.Arg251Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,558,908 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00029 ( 14 hom. )

Consequence

HCAR3
NM_006018.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

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:

ENSG00000256249 (HGNC:):

ENSG00000256249 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042319357).

BS2

High Homozygotes in GnomAdExome4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCAR3	NM_006018.3 linkuse as main transcript	c.752G>A	p.Arg251Gln	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.752G>A	p.Arg251Gln	missense_variant	1/1	6	NM_006018.3	ENSP00000436714.2		P49019
ENSG00000256249	ENST00000543611.1 linkuse as main transcript	n.*7C>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000533

AC:

AN:

148302

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000655

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000223

Gnomad OTH

AF:

0.00150

GnomAD3 exomes

AF:

0.000462

AC:

109

AN:

235734

Hom.:

AF XY:

0.000422

AC XY:

AN XY:

128042

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.00140

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000297

Gnomad OTH exome

AF:

0.00223

GnomAD4 exome

AF:

0.000285

AC:

402

AN:

1410490

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

195

AN XY:

702132

show subpopulations

Gnomad4 AFR exome

AF:

0.000909

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000512

Gnomad4 SAS exome

AF:

0.0000352

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000233

Gnomad4 OTH exome

AF:

0.000716

GnomAD4 genome

AF:

0.000532

AC:

AN:

148418

Hom.:

Cov.:

AF XY:

0.000567

AC XY:

AN XY:

72248

show subpopulations

Gnomad4 AFR

AF:

0.000653

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000223

Gnomad4 OTH

AF:

0.00149

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000771

ESP6500AA

AF:

0.000920

AC:

ESP6500EA

AF:

0.000468

AC:

ExAC

AF:

0.000372

AC:

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

Mar 14, 2023

The c.752G>A (p.R251Q) alteration is located in exon 1 (coding exon 1) of the HCAR3 gene. This alteration results from a G to A substitution at nucleotide position 752, causing the arginine (R) at amino acid position 251 to be replaced by a glutamine (Q). 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

0.26

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0091

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.81

M_CAP

Benign

0.018

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

REVEL

Benign

0.16

Sift

Benign

0.077

Sift4G

Benign

0.17

Vest4

0.49

MVP

0.42

MPC

1.8

ClinPred

0.035

GERP RS

3.3

Varity_R

0.16

gMVP

0.18

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