6-63720626-A-G

Variant names:

• chr6-63720626-A-G
• rs137853190
• NM_001142800.2:c.9405T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001142800.2(EYS):​c.9405T>C​(p.Tyr3135Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,354,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: EYS NM_001142800.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.41
• 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]

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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-63720626-A-G is Benign according to our data. Variant chr6-63720626-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1626869.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.41 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.9405T>C	p.Tyr3135Tyr	synonymous	Exon 43 of 43	NP_001136272.1
	PHF3	NM_001370348.2	MANE Select	c.*6918A>G		3_prime_UTR	Exon 16 of 16	NP_001357277.1
	EYS	NM_001292009.2		c.9468T>C	p.Tyr3156Tyr	synonymous	Exon 44 of 44	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.9405T>C	p.Tyr3135Tyr	synonymous	Exon 43 of 43	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.9468T>C	p.Tyr3156Tyr	synonymous	Exon 44 of 44	ENSP00000359655.3
	PHF3	ENST00000262043.8	TSL:5 MANE Select	c.*6918A>G		3_prime_UTR	Exon 16 of 16	ENSP00000262043.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1354866 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 665040

African (AFR) AF: 0.00 AC: 0 AN: 29778

American (AMR) AF: 0.00 AC: 0 AN: 29150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22502

East Asian (EAS) AF: 0.00 AC: 0 AN: 35348

South Asian (SAS) AF: 0.00 AC: 0 AN: 70488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5448

European-Non Finnish (NFE) AF: 9.45e-7 AC: 1 AN: 1058164

Other (OTH) AF: 0.00 AC: 0 AN: 56160

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 21, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.5
DANN	Benign	0.86
PhyloP100		2.4

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: rs137853190; hg19: chr6-64430522;