rs281875234

chr17-38334016-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PS1_Moderate PM1 PM2 PP5

The NM_001004334.4(GPR179):c.1807C>T(p.His603Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR179 NM_001004334.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 8.84

Genes affected

GPR179 (HGNC:31371): (G protein-coupled receptor 179) This gene encodes a member of the glutamate receptor subfamily of G protein-coupled receptors. The encoded protein has an EGF-like calcium binding domain and a seven transmembrane domain in the N-terminal region of the protein. Mutations in this gene are associated with congenital stationary night blindness type 1E. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PS1: Transcript NM_001004334.4 (GPR179) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• PM1: In a topological_domain Extracellular (size 12) in uniprot entity GP179_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001004334.4
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-38334016-G-A is Pathogenic according to our data. Variant chr17-38334016-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 31200.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-38334016-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR179	NM_001004334.4	c.1807C>T	p.His603Tyr	missense_variant	9/11	ENST00000616987.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR179	ENST00000616987.5	c.1807C>T	p.His603Tyr	missense_variant	9/11	1	NM_001004334.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461614 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727108

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital stationary night blindness 1E Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 10, 2012

- -

not provided Other:1

not provided, no classification provided

literature only

UniProtKB/Swiss-Prot

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.31	T
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.79	T
Sift4G	Uncertain	0.0030	D;D
Vest4		0.60
MutPred		0.52		Loss of sheet (P = 0.0315);.;
MVP		0.18
ClinPred		0.99	D
GERP RS		4.0
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs281875234; hg19: chr17-36489899;