rs1042454

chr10-84252957-C-Achr10-84252957-C-Gchr10-84252957-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001012720.2(RGR):c.459C>A(p.Tyr153Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y153Y) has been classified as Benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGR NM_001012720.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

Genes affected

RGR (HGNC:9990): (retinal G protein coupled receptor) This gene encodes a putative retinal G-protein coupled receptor. The gene is a member of the opsin subfamily of the 7 transmembrane, G-protein coupled receptor 1 family. Like other opsins which bind retinaldehyde, it contains a conserved lysine residue in the seventh transmembrane domain. The protein acts as a photoisomerase to catalyze the conversion of all-trans-retinal to 11-cis-retinal. The reverse isomerization occurs with rhodopsin in retinal photoreceptor cells. The protein is exclusively expressed in tissue adjacent to retinal photoreceptor cells, the retinal pigment epithelium and Mueller cells. This gene may be associated with autosomal recessive and autosomal dominant retinitis pigmentosa (arRP and adRP, respectively). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001012720.2 Downstream stopcodon found after 303 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGR	NM_001012720.2	c.459C>A	p.Tyr153Ter	stop_gained	4/7	ENST00000652092.2
RGR	NM_002921.4	c.471C>A	p.Tyr157Ter	stop_gained	4/7
RGR	NM_001012722.2	c.459C>A	p.Tyr153Ter	stop_gained	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGR	ENST00000652092.2	c.459C>A	p.Tyr153Ter	stop_gained	4/7		NM_001012720.2	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
Cadd	Pathogenic	37
Dann	Uncertain	1.0
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.72	D
MutationTaster	Benign	3.8e-21	P;P
Vest4		0.90
GERP RS		2.6

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: rs1042454; hg19: chr10-86012713;