rs886043488

Positions:

• chr17-38339516-CACCTG-CGTAGATCA

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_001004334.4(GPR179):​c.799_803delinsTGATCTAC​(p.Gln267_Val268delinsTer) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR179 NM_001004334.4 stop_gained
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2
• Conservation: PhyloP100: 8.25

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 Pathogenic. Variant got 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-38339517-ACCTG-GTAGATCA is Pathogenic according to our data. Variant chr17-38339517-ACCTG-GTAGATCA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 286815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR179	NM_001004334.4	c.799_803delinsTGATCTAC	p.Gln267_Val268delinsTer	stop_gained	2/11	ENST00000616987.5	NP_001004334.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR179	ENST00000616987.5	c.799_803delinsTGATCTAC	p.Gln267_Val268delinsTer	stop_gained	2/11	1	NM_001004334.4	ENSP00000483469	P1
GPR179	ENST00000610867.1	n.857_861delinsTGATCTAC		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 12, 2016

- -

Congenital stationary night blindness Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 02, 2017

The p.Gln267X (NM_001004334.2 c.799_803delinsTGATCTAC) (also referred to as c.79 9_803delCAGGTinsTGATCTAC p.Gln267_Leu602delinsTer) variant in GPR179 has not bee n previously reported in the literature, but has been reported in ClinVar as pat hogenic by one laboratory (Variation ID#286815). It is absent from large populat ion studies, though the ability of these studies to accurately detect indels may be limited. This deletion/insertion variant introduces a premature termination codon at position 267, which is predicted to lead to a truncated or absent prote in. Biallelic loss of function of the GPR179 gene has been associated with conge nital stationary night blindness. In summary, although additional studies are re quired to fully establish a null effect, this variant is likely pathogenic for c ongenital stationary night blindness in an autosomal recessive manner based upon its predicted impact on the protein. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886043488; hg19: chr17-36495400;