6-63806194-G-A

Variant names:

• chr6-63806194-G-A
• rs780311041
• NM_001142800.2:c.7407C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001142800.2(EYS):​c.7407C>T​(p.Gly2469Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,768 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. Synonymous variant affecting the same amino acid position (i.e. G2469G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: EYS NM_001142800.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.012).
• BP7: Synonymous conserved (PhyloP=-0.434 with no splicing effect.

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.7407C>T	p.Gly2469Gly	synonymous	Exon 37 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.7407C>T	p.Gly2469Gly	synonymous	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.7407C>T	p.Gly2469Gly	synonymous	Exon 37 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.7407C>T	p.Gly2469Gly	synonymous	Exon 37 of 44	ENSP00000359655.3	Q5T1H1-3
	EYS	ENST00000398580.3	TSL:5	c.720C>T	p.Gly240Gly	synonymous	Exon 5 of 10	ENSP00000381585.3	H0Y3Q4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000641 AC: 1 AN: 156056 AF XY: 0.0000121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398768 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689918

African (AFR) AF: 0.00 AC: 0 AN: 31584

American (AMR) AF: 0.00 AC: 0 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 35714

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078510

Other (OTH) AF: 0.00 AC: 0 AN: 57978

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.3
DANN	Benign	0.72
PhyloP100		-0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs780311041; hg19: chr6-64516087; COSMIC: COSV65545436; COSMIC: COSV65545436;