chr6-63762377-A-T

Variant names:

• chr6-63762377-A-T
• rs4710257
• NM_001142800.2:c.8071+84T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142800.2(EYS):​c.8071+84T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544
• Publications: 5 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]

PHF3 (HGNC:8921): (PHD finger protein 3) This gene encodes a member of a PHD finger-containing gene family. This gene may function as a transcription factor and may be involved in glioblastomas development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.8071+84T>A		intron_variant	Intron 41 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.8071+84T>A		intron_variant	Intron 41 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.8071+84T>A		intron_variant	Intron 41 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.8071+84T>A		intron_variant	Intron 41 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.1384+84T>A		intron_variant	Intron 9 of 9	5		ENSP00000381585.3
PHF3	ENST00000505138.1	c.362-15689A>T		intron_variant	Intron 3 of 4	3		ENSP00000421417.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.87e-7 AC: 1 AN: 1127804 Hom.: 0 AF XY: 0.00000177 AC XY: 1 AN XY: 565088

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24382

American (AMR) AF: 0.00 AC: 0 AN: 26030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21922

East Asian (EAS) AF: 0.00 AC: 0 AN: 34198

South Asian (SAS) AF: 0.00 AC: 0 AN: 67156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3494

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 854192

Other (OTH) AF: 0.0000207 AC: 1 AN: 48278

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.77
PhyloP100		0.54

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: rs4710257; hg19: chr6-64472270;