rs2136315619

Variant names:

• chr12-12661776-C-G
• rs2136315619
• NM_006143.3:c.673G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-12661776-C-G
• chr12-12661776-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006143.3(GPR19):​c.673G>C​(p.Val225Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/21 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. V225I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR19 NM_006143.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07591382).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006143.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR19	NM_006143.3	MANE Select	c.673G>C	p.Val225Leu	missense	Exon 4 of 4	NP_006134.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR19	ENST00000651487.1	MANE Select	c.673G>C	p.Val225Leu	missense	Exon 4 of 4	ENSP00000498976.1
	GPR19	ENST00000332427.6	TSL:4	c.673G>C	p.Val225Leu	missense	Exon 4 of 4	ENSP00000333744.2
	GPR19	ENST00000540510.1	TSL:2	c.673G>C	p.Val225Leu	missense	Exon 2 of 2	ENSP00000441832.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.9
DANN	Benign	0.73
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.80	N
PhyloP100		-0.28
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.025
Sift	Benign	0.091	T
Sift4G	Benign	0.17	T
Polyphen		0.015	B
Vest4		0.068
MutPred		0.39		Gain of helix (P = 0.132)
MVP		0.36
MPC		0.39
ClinPred		0.11	T
GERP RS		0.82
Varity_R		0.076
Mutation Taster		=95/5	polymorphism

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: rs2136315619; hg19: chr12-12814710;