12-12661947-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR19	NM_006143.3	c.502G>A	p.Val168Ile	missense_variant	4/4	ENST00000651487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR19	ENST00000651487.1	c.502G>A	p.Val168Ile	missense_variant	4/4		NM_006143.3	P1
GPR19	ENST00000332427.6	c.502G>A	p.Val168Ile	missense_variant	4/4	4		P1
GPR19	ENST00000540510.1	c.502G>A	p.Val168Ile	missense_variant	2/2	2		P1

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

GnomAD3 exomes AF: 0.000907 AC: 228 AN: 251402 Hom.: 3 AF XY: 0.000640 AC XY: 87 AN XY: 135872

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 SAS exome AF: 0.0000980

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

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.000878

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

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000652 Hom.: 0

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 20, 2018

- -

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
MetaRNN	Benign	0.0099	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	D;D
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs115836857; hg19: chr12-12814881; COSMIC: COSV60124064; COSMIC: COSV60124064;