rs201580493

Variant names:

• chr6-64307042-A-C
• NM_001142800.2:c.6119T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-64307042-A-C
• chr6-64307042-A-G
• chr6-64307042-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142800.2(EYS):​c.6119T>G​(p.Val2040Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000719 in 1,390,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V2040D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: EYS NM_001142800.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35035264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6119T>G	p.Val2040Gly	missense_variant	Exon 30 of 43	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6119T>G	p.Val2040Gly	missense_variant	Exon 30 of 44		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6119T>G	p.Val2040Gly	missense_variant	Exon 30 of 43	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6119T>G	p.Val2040Gly	missense_variant	Exon 30 of 44	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390354 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 686330

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.33e-7

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	Uncertain	0.44
BayesDel_addAF	Benign	-0.0024	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.30	T;T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.28
MutPred		0.54		Loss of stability (P = 0.0137);Loss of stability (P = 0.0137);
MVP		0.66
MPC		0.058
ClinPred		0.94	D
GERP RS		5.1
Varity_R		0.41
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: chr6-65016935;