chr6-65295995-C-G

Position:

• chr6-65295995-C-G

Variant summary

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

The NM_001142800.2(EYS):​c.1891G>C​(p.Gly631Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G631S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EYS NM_001142800.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

Genes affected

EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

EYS (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.1891G>C	p.Gly631Arg	missense_variant	12/43	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.1891G>C	p.Gly631Arg	missense_variant	12/44		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.1891G>C	p.Gly631Arg	missense_variant	12/43	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.1891G>C	p.Gly631Arg	missense_variant	12/44	1		ENSP00000359655.3
EYS	ENST00000370615.3	n.329G>C		non_coding_transcript_exon_variant	2/2	3
EYS	ENST00000447127.1	n.347G>C		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.6
DANN	Benign	0.70
DEOGEN2	Benign	0.027	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.44	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.059	T;T
Polyphen		0.090	B;.
Vest4		0.24
MutPred		0.92		Loss of glycosylation at S630 (P = 0.0951);Loss of glycosylation at S630 (P = 0.0951);
MVP		0.12
MPC		0.0096
ClinPred		0.080	T
GERP RS		1.7
Varity_R		0.038
gMVP		0.74

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: rs9342464; hg19: chr6-66005888;