NM_006583.5:c.823A>C

Variant names:

• chr4-109842571-A-C
• NM_006583.5:c.823A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006583.5(RRH):​c.823A>C​(p.Met275Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RRH NM_006583.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

RRH (HGNC:10450): (retinal pigment epithelium-derived rhodopsin homolog) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This gene belongs to the seven-exon subfamily of mammalian opsin genes that includes opsin 5 and retinal G protein coupled receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11464456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRH	NM_006583.5	c.823A>C	p.Met275Leu	missense_variant	Exon 6 of 7	ENST00000317735.7	NP_006574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRH	ENST00000317735.7	c.823A>C	p.Met275Leu	missense_variant	Exon 6 of 7	1	NM_006583.5	ENSP00000314992.4
RRH	ENST00000652276.1	c.444-1512A>C		intron_variant	Intron 3 of 3			ENSP00000498977.1
RRH	ENST00000650907.1	n.1881A>C		non_coding_transcript_exon_variant	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461552 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727094

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.20
DANN	Benign	0.53
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.59	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.073
Sift	Benign	0.54	T
Sift4G	Benign	0.42	T
Polyphen		0.0010	B
Vest4		0.39
MutPred		0.48		Gain of catalytic residue at M275 (P = 0.0194);
MVP		0.18
MPC		0.024
ClinPred		0.12	T
GERP RS		1.7
Varity_R		0.15
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-110763727;