6-63720623-A-G

Variant names:

• chr6-63720623-A-G
• NM_001142800.2:c.9408T>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.9408T>C​(p.Asp3136Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,351,156 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: 33)
  • 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: 0.693
• 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=-0.57).
• BP6: Variant 6-63720623-A-G is Benign according to our data. Variant chr6-63720623-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1133623.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.693 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.9408T>C	p.Asp3136Asp	synonymous_variant	Exon 43 of 43	ENST00000503581.6	NP_001136272.1
PHF3	NM_001370348.2	c.*6915A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.9408T>C	p.Asp3136Asp	synonymous_variant	Exon 43 of 43	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.9471T>C	p.Asp3157Asp	synonymous_variant	Exon 44 of 44	1		ENSP00000359655.3
PHF3	ENST00000262043.8	c.*6915A>G		3_prime_UTR_variant	Exon 16 of 16	5	NM_001370348.2	ENSP00000262043.4
PHF3	ENST00000505138.1	c.361+9261A>G		intron_variant	Intron 3 of 4	3		ENSP00000421417.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.40e-7 AC: 1 AN: 1351156 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 662894

African (AFR) AF: 0.00 AC: 0 AN: 29734

American (AMR) AF: 0.00 AC: 0 AN: 28912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22312

East Asian (EAS) AF: 0.00 AC: 0 AN: 35334

South Asian (SAS) AF: 0.0000143 AC: 1 AN: 69856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5430

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055812

Other (OTH) AF: 0.00 AC: 0 AN: 56054

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 27, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.9
DANN	Benign	0.84
PhyloP100		0.69

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

hg19: chr6-64430519;