rs138082392
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_133444.3(ZNF526):c.825C>T(p.Cys275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,613,994 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 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 0 hom. )
Consequence
ZNF526
NM_133444.3 synonymous
NM_133444.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.978
Genes affected
ZNF526 (HGNC:29415): (zinc finger protein 526) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 19-42225228-C-T is Benign according to our data. Variant chr19-42225228-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 437386.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BP7
?
Synonymous conserved (PhyloP=0.978 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF526 | NM_133444.3 | c.825C>T | p.Cys275= | synonymous_variant | 3/3 | ENST00000301215.8 | |
ZNF526 | NM_001314033.3 | c.825C>T | p.Cys275= | synonymous_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF526 | ENST00000301215.8 | c.825C>T | p.Cys275= | synonymous_variant | 3/3 | 1 | NM_133444.3 | P1 | |
ZNF526 | ENST00000710326.1 | c.825C>T | p.Cys275= | synonymous_variant | 3/3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000240 AC: 60AN: 250452Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135528
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GnomAD4 exome AF: 0.000285 AC: 416AN: 1461774Hom.: 0 Cov.: 32 AF XY: 0.000268 AC XY: 195AN XY: 727174
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GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74360
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 06, 2015 | - - |
ZNF526-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 15, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at