4-109828059-A-T

Variant names:

• chr4-109828059-A-T
• rs370590600
• NM_006583.5:c.32A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006583.5(RRH):​c.32A>T​(p.Asp11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D11G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RRH NM_006583.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.183453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006583.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRH	NM_006583.5	MANE Select	c.32A>T	p.Asp11Val	missense	Exon 1 of 7	NP_006574.1	O14718

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRH	ENST00000317735.7	TSL:1 MANE Select	c.32A>T	p.Asp11Val	missense	Exon 1 of 7	ENSP00000314992.4	O14718

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.090
Sift	Benign	0.071	T
Sift4G	Benign	0.15	T
Polyphen		0.29	B
Vest4		0.40
MutPred		0.14		Gain of methylation at K13 (P = 0.0467)
MVP		0.76
MPC		0.029
ClinPred		0.15	T
GERP RS		-0.17
PromoterAI		0.0046	Neutral
Varity_R		0.096
gMVP		0.62
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs370590600; hg19: chr4-110749215;