17-38337665-C-T

Variant names:

• chr17-38337665-C-T
• rs189931659
• NM_001004334.4:c.959G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001004334.4(GPR179):​c.959G>A​(p.Arg320Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,613,516 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (11 hom.)
• Consequence: GPR179 NM_001004334.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:4
• Conservation: PhyloP100: -0.111

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008164585).
• BP6: Variant 17-38337665-C-T is Benign according to our data. Variant chr17-38337665-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 196293.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=3}. Variant chr17-38337665-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00202 (308/152372) while in subpopulation NFE AF= 0.00342 (233/68040). AF 95% confidence interval is 0.00306. There are 0 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR179	NM_001004334.4	c.959G>A	p.Arg320Gln	missense_variant	Exon 3 of 11	ENST00000616987.5	NP_001004334.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR179	ENST00000616987.5	c.959G>A	p.Arg320Gln	missense_variant	Exon 3 of 11	1	NM_001004334.4	ENSP00000483469.2

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 308 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000940

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00342

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00194 AC: 483 AN: 248770 Hom.: 0 AF XY: 0.00201 AC XY: 272 AN XY: 135038

Gnomad AFR exome AF: 0.000777

Gnomad AMR exome AF: 0.000817

Gnomad ASJ exome AF: 0.00529

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000883

Gnomad FIN exome AF: 0.000418

Gnomad NFE exome AF: 0.00299

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00334 AC: 4873 AN: 1461144 Hom.: 11 Cov.: 31 AF XY: 0.00321 AC XY: 2332 AN XY: 726876

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.000988

Gnomad4 ASJ exome AF: 0.00536

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000801

Gnomad4 FIN exome AF: 0.000618

Gnomad4 NFE exome AF: 0.00397

Gnomad4 OTH exome AF: 0.00253

GnomAD4 genome AF: 0.00202 AC: 308 AN: 152372 Hom.: 0 Cov.: 33 AF XY: 0.00180 AC XY: 134 AN XY: 74508

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00342

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00253 Hom.: 0

Bravo AF: 0.00204

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.00127 AC: 5

ESP6500EA AF: 0.00398 AC: 33

ExAC AF: 0.00194 AC: 235

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00278

EpiControl AF: 0.00267

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3 Benign:4

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:2 Benign:2

Jun 12, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GPR179: BP4 -

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 11, 2016

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital stationary night blindness 1E Uncertain:1 Benign:1

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

GPR179-related disorder Benign:1

Jul 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	1.0
Eigen	Benign	-0.057
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.0082	T;T
MetaSVM	Benign	-0.68	T
PrimateAI	Benign	0.26	T
Sift4G	Uncertain	0.059	T;T
Vest4		0.17
MVP		0.048
ClinPred		0.036	T
GERP RS		3.1
gMVP		0.77

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: rs189931659; hg19: chr17-36493548;