6-63806209-A-T

Variant names:

• chr6-63806209-A-T
• rs754984757
• NM_001142800.2:c.7392T>A

Variant summary

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

The NM_001142800.2(EYS):​c.7392T>A​(p.Phe2464Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EYS NM_001142800.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 publications found

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]

SCAT8 (HGNC:40967): (S-phase cancer associated transcript 8)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. 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
	EYS	NM_001142800.2	MANE Select	c.7392T>A	p.Phe2464Leu	missense	Exon 37 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.7392T>A	p.Phe2464Leu	missense	Exon 37 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.7392T>A	p.Phe2464Leu	missense	Exon 37 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.7392T>A	p.Phe2464Leu	missense	Exon 37 of 44	ENSP00000359655.3	Q5T1H1-3
	EYS	ENST00000398580.3	TSL:5	c.705T>A	p.Phe235Leu	missense	Exon 5 of 10	ENSP00000381585.3	H0Y3Q4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.047
Eigen_PC	Benign	-0.0097
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.7
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.24
Sift	Benign	0.036	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.53
MutPred		0.72		Loss of catalytic residue at F2464 (P = 0.0573)
MVP		0.12
MPC		0.017
ClinPred		0.94	D
GERP RS		2.3
Varity_R		0.17
gMVP		0.27
Mutation Taster		=35/65	disease causing

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: rs754984757; hg19: chr6-64516102;