chr12-56996356-T-C

Position:

• chr12-56996356-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007264.4(GPR182):​c.1147T>C​(p.Phe383Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR182 NM_007264.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

Genes affected

GPR182 (HGNC:13708): (G protein-coupled receptor 182) Adrenomedullin is a potent vasodilator peptide that exerts major effects on cardiovascular function. This gene encodes a seven-transmembrane protein that belongs to the family 1 of G-protein coupled receptors. Studies of the rat counterpart suggest that the encoded protein may function as a receptor for adrenomedullin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054773033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR182	NM_007264.4	c.1147T>C	p.Phe383Leu	missense_variant	2/2	ENST00000300098.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR182	ENST00000300098.3	c.1147T>C	p.Phe383Leu	missense_variant	2/2	1	NM_007264.4	P1
GPR182	ENST00000556850.1	c.100T>C	p.Phe34Leu	missense_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.2
DANN	Benign	0.82
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.074
Sift	Benign	0.17	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.16		Gain of glycosylation at S382 (P = 0.0582);
MVP		0.11
MPC		0.18
ClinPred		0.096	T
GERP RS		-0.83
Varity_R		0.082
gMVP		0.25

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: chr12-57390140;