6-63720599-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP5BP4BP7

The NM_001142800.2(EYS):c.9432A>G(p.Thr3144Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,472,372 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

EYS
NM_001142800.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1

Conservation

PhyloP100: -0.940

Publications

0 publications found

Variant links:

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]

EYS links:

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]

PHF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PP5

Variant 6-63720599-T-C is Pathogenic according to our data. Variant chr6-63720599-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2167040.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=1}.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91). . Strength limited to SUPPORTING due to the PP5.

BP7

Synonymous conserved (PhyloP=-0.94 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.9432A>G	p.Thr3144Thr	synonymous_variant	Exon 43 of 43	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
PHF3	NM_001370348.2 link	c.*6891T>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EYS	ENST00000503581.6 link	c.9432A>G	p.Thr3144Thr	synonymous_variant	Exon 43 of 43	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.9495A>G	p.Thr3165Thr	synonymous_variant	Exon 44 of 44	1		ENSP00000359655.3	Q5T1H1-3
PHF3	ENST00000262043.8 link	c.*6891T>C		3_prime_UTR_variant	Exon 16 of 16	5	NM_001370348.2	ENSP00000262043.4	Q92576-1
PHF3	ENST00000505138.1 link	c.361+9237T>C		intron_variant	Intron 3 of 4	3		ENSP00000421417.1	H0Y8L0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

102440

AF XY:

0.00

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:

0.0000212

AC:

AN:

1320220

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

645852

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28792

American (AMR)

AF:

0.00

AC:

AN:

24694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20620

East Asian (EAS)

AF:

0.0000284

AC:

AN:

35180

South Asian (SAS)

AF:

0.00

AC:

AN:

64992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46680

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5272

European-Non Finnish (NFE)

AF:

0.0000260

AC:

AN:

1039224

Other (OTH)

AF:

0.00

AC:

AN:

54766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5208

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Retinal dystrophy

Pathogenic:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

not provided

Uncertain:1

Jul 20, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces threonine, which is neutral and polar, with threonine, which is neutral and polar, at codon 3144 of the EYS protein (Silent). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EYS-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.25

(source)

DANN

Benign

0.67

PhyloP100

-0.94

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

Publications

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6-63720599-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over