rs115836857

Variant names:

• chr12-12661947-C-G
• rs115836857
• NM_006143.3:c.502G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-12661947-C-G
• chr12-12661947-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006143.3(GPR19):​c.502G>C​(p.Val168Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V168I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR19 NM_006143.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03
• Publications: 0 publications found

Genes affected

GPR19 (HGNC:4473): (G protein-coupled receptor 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000257004 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32209012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR19	NM_006143.3	c.502G>C	p.Val168Leu	missense_variant	Exon 4 of 4	ENST00000651487.1	NP_006134.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR19	ENST00000651487.1	c.502G>C	p.Val168Leu	missense_variant	Exon 4 of 4		NM_006143.3	ENSP00000498976.1
GPR19	ENST00000332427.6	c.502G>C	p.Val168Leu	missense_variant	Exon 4 of 4	4		ENSP00000333744.2
GPR19	ENST00000540510.1	c.502G>C	p.Val168Leu	missense_variant	Exon 2 of 2	2		ENSP00000441832.1
ENSG00000257004	ENST00000817557.1	n.465+3983C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	0.066
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.86	.;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M
PhyloP100		6.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.63	N;N
REVEL	Benign	0.22
Sift	Benign	0.13	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.25	B;B
Vest4		0.50
MutPred		0.63		Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);
MVP		0.23
MPC		0.57
ClinPred		0.66	D
GERP RS		5.7
Varity_R		0.24
Mutation Taster		=47/53	disease causing

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: rs115836857; hg19: chr12-12814881;