12-12661947-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006143.3(GPR19):​c.502G>A​(p.Val168Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000685 in 1,614,204 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00035 (2 hom.)
• Consequence: GPR19 NM_006143.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.03
• Publications: 3 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009867579).
• BP6: Variant 12-12661947-C-T is Benign according to our data. Variant chr12-12661947-C-T is described in ClinVar as [Benign]. Clinvar id is 713760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR19	NM_006143.3	c.502G>A	p.Val168Ile	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>A	p.Val168Ile	missense_variant	Exon 4 of 4		NM_006143.3	ENSP00000498976.1
GPR19	ENST00000332427.6	c.502G>A	p.Val168Ile	missense_variant	Exon 4 of 4	4		ENSP00000333744.2
GPR19	ENST00000540510.1	c.502G>A	p.Val168Ile	missense_variant	Exon 2 of 2	2		ENSP00000441832.1
ENSG00000257004	ENST00000817557.1	n.465+3983C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 595 AN: 152212 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000907 AC: 228 AN: 251402 AF XY: 0.000640

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000347 AC: 508 AN: 1461874 Hom.: 2 Cov.: 35 AF XY: 0.000282 AC XY: 205 AN XY: 727242

African (AFR) AF: 0.0123 AC: 412 AN: 33480

American (AMR) AF: 0.000470 AC: 21 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: 0.0000580 AC: 5 AN: 86254

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

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112000

Other (OTH) AF: 0.000878 AC: 53 AN: 60396

GnomAD4 genome AF: 0.00392 AC: 597 AN: 152330 Hom.: 9 Cov.: 33 AF XY: 0.00383 AC XY: 285 AN XY: 74492

African (AFR) AF: 0.0137 AC: 569 AN: 41560

American (AMR) AF: 0.00137 AC: 21 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68044

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00142 Hom.: 3

Bravo AF: 0.00420

ESP6500AA AF: 0.0123 AC: 54

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00115 AC: 140

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Benign	0.070	T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	.;T
MetaRNN	Benign	0.0099	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
PhyloP100		6.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.050	N;N
REVEL	Benign	0.19
Sift	Benign	0.22	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.98	D;D
Vest4		0.38
MVP		0.15
MPC		0.50
ClinPred		0.041	T
GERP RS		5.7
Varity_R		0.17
Mutation Taster		=94/6	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: rs115836857; hg19: chr12-12814881; COSMIC: COSV60124064; COSMIC: COSV60124064;