chr6-63720626-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001142800.2(EYS):ā€‹c.9405T>Cā€‹(p.Tyr3135=) 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.4e-7 ( 0 hom. )

Consequence

EYS
NM_001142800.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.41
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 1626869.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.41 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EYSNM_001142800.2 linkuse as main transcriptc.9405T>C p.Tyr3135= synonymous_variant 43/43 ENST00000503581.6 NP_001136272.1
PHF3NM_001370348.2 linkuse as main transcriptc.*6918A>G 3_prime_UTR_variant 16/16 ENST00000262043.8 NP_001357277.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EYSENST00000503581.6 linkuse as main transcriptc.9405T>C p.Tyr3135= synonymous_variant 43/435 NM_001142800.2 ENSP00000424243 A2Q5T1H1-1
EYSENST00000370621.7 linkuse as main transcriptc.9468T>C p.Tyr3156= synonymous_variant 44/441 ENSP00000359655 P2Q5T1H1-3
PHF3ENST00000262043.8 linkuse as main transcriptc.*6918A>G 3_prime_UTR_variant 16/165 NM_001370348.2 ENSP00000262043 P1Q92576-1
PHF3ENST00000505138.1 linkuse as main transcriptc.363+9264A>G intron_variant 3 ENSP00000421417

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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.45e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 21, 2023- -

Computational scores

Source: dbNSFP v4.3

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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-64430522; API