NM_006143.3:c.776C>A

Variant names:

• chr12-12661673-G-T
• NM_006143.3:c.776C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006143.3(GPR19):​c.776C>A​(p.Thr259Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR19 NM_006143.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.91

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR19	NM_006143.3	c.776C>A	p.Thr259Lys	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.776C>A	p.Thr259Lys	missense_variant	Exon 4 of 4		NM_006143.3	ENSP00000498976.1
GPR19	ENST00000332427.6	c.776C>A	p.Thr259Lys	missense_variant	Exon 4 of 4	4		ENSP00000333744.2
GPR19	ENST00000540510.1	c.776C>A	p.Thr259Lys	missense_variant	Exon 2 of 2	2		ENSP00000441832.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461552 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.088	T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.22	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.99	D;D
Vest4		0.54
MutPred		0.50		Loss of phosphorylation at T259 (P = 0.0258);Loss of phosphorylation at T259 (P = 0.0258);
MVP		0.64
MPC		1.0
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-12814607;