12-122716878-T-G

Variant names:

• chr12-122716878-T-G
• rs3825163
• NM_006018.3:c.-141A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006018.3(HCAR3):​c.-141A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000732 in 136,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000073 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HCAR3 NM_006018.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006018.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCAR3	NM_006018.3	MANE Select	c.-141A>C		upstream_gene	N/A	NP_006009.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCAR3	ENST00000528880.3	TSL:6 MANE Select	c.-141A>C		upstream_gene	N/A	ENSP00000436714.2

Frequencies

GnomAD3 genomes AF: 0.00000732 AC: 1 AN: 136560 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000302

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 723628 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 364944

African (AFR) AF: 0.00 AC: 0 AN: 17818

American (AMR) AF: 0.00 AC: 0 AN: 17310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14228

East Asian (EAS) AF: 0.00 AC: 0 AN: 31326

South Asian (SAS) AF: 0.00 AC: 0 AN: 41794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3514

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 520486

Other (OTH) AF: 0.00 AC: 0 AN: 33302

GnomAD4 genome AF: 0.00000732 AC: 1 AN: 136560 Hom.: 0 Cov.: 28 AF XY: 0.0000153 AC XY: 1 AN XY: 65430

African (AFR) AF: 0.00 AC: 0 AN: 35082

American (AMR) AF: 0.00 AC: 0 AN: 12546

Ashkenazi Jewish (ASJ) AF: 0.000302 AC: 1 AN: 3312

East Asian (EAS) AF: 0.00 AC: 0 AN: 4662

South Asian (SAS) AF: 0.00 AC: 0 AN: 4302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65174

Other (OTH) AF: 0.00 AC: 0 AN: 1844

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Benign	0.64
PhyloP100		0.57
PromoterAI		0.34	Neutral

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

Other links and lift over

dbSNP: rs3825163; hg19: chr12-123201425;