rs61733942

Variant names:

• chr12-12661218-G-C
• rs61733942
• NM_006143.3:c.1231C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-12661218-G-C
• chr12-12661218-G-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.1231C>G​(p.Pro411Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. P411T) 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: 8.13
• 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=0.35130966).

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.1231C>G	p.Pro411Ala	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.1231C>G	p.Pro411Ala	missense	Exon 4 of 4	ENSP00000498976.1
	GPR19	ENST00000332427.6	TSL:4	c.1231C>G	p.Pro411Ala	missense	Exon 4 of 4	ENSP00000333744.2
	GPR19	ENST00000540510.1	TSL:2	c.1231C>G	p.Pro411Ala	missense	Exon 2 of 2	ENSP00000441832.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		8.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Benign	0.21	T
Polyphen		0.97	D
Vest4		0.51
MutPred		0.30		Loss of glycosylation at P411 (P = 0.035)
MVP		0.24
MPC		0.78
ClinPred		0.70	D
GERP RS		5.6
Varity_R		0.14
Mutation Taster		=50/50

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: rs61733942; hg19: chr12-12814152;