ENST00000334937.8:c.189C>T
Variant names:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000334937.8(ZNF81):c.189C>T(p.Asp63Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,204,317 control chromosomes in the GnomAD database, including 357 homozygotes. There are 9,876 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.020 ( 34 hom., 708 hem., cov: 22)
Exomes 𝑓: 0.026 ( 323 hom. 9168 hem. )
Consequence
ZNF81
ENST00000334937.8 synonymous
ENST00000334937.8 synonymous
Scores
2
Splicing: ADA: 0.0004466
2
Clinical Significance
Conservation
PhyloP100: -0.0740
Genes affected
ZNF81 (HGNC:13156): (zinc finger protein 81) This gene encodes a protein that likely functions as a transcription factor. The protein contains an N-terminal KRAB domain and several C2H2-type zinc finger motifs. Mutations in this gene cause an X-linked form of intellectual disability (MRX45). Microduplication of a region of chromosome X including this gene has also been associated with other forms of intellectual disability. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant X-47888133-C-T is Benign according to our data. Variant chrX-47888133-C-T is described in ClinVar as [Benign]. Clinvar id is 95449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47888133-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.074 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0197 (2184/110984) while in subpopulation NFE AF= 0.0284 (1505/52971). AF 95% confidence interval is 0.0272. There are 34 homozygotes in gnomad4. There are 708 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 34 XL gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF81 | ENST00000334937.8 | c.189C>T | p.Asp63Asp | synonymous_variant | Exon 4 of 4 | 1 | ENSP00000334641.4 | |||
ZNF81 | ENST00000338637.13 | c.181+8C>T | splice_region_variant, intron_variant | Intron 3 of 4 | 3 | NM_007137.5 | ENSP00000341151.7 | |||
ZNF81 | ENST00000376954.6 | c.181+8C>T | splice_region_variant, intron_variant | Intron 4 of 5 | 5 | ENSP00000366153.1 | ||||
ZNF81 | ENST00000376950.4 | c.181+8C>T | splice_region_variant, intron_variant | Intron 3 of 4 | 5 | ENSP00000366149.4 |
Frequencies
GnomAD3 genomes AF: 0.0197 AC: 2183AN: 110933Hom.: 34 Cov.: 22 AF XY: 0.0214 AC XY: 708AN XY: 33129
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GnomAD3 exomes AF: 0.0215 AC: 3664AN: 170744Hom.: 64 AF XY: 0.0212 AC XY: 1211AN XY: 57246
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GnomAD4 exome AF: 0.0260 AC: 28381AN: 1093333Hom.: 323 Cov.: 31 AF XY: 0.0255 AC XY: 9168AN XY: 359297
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GnomAD4 genome AF: 0.0197 AC: 2184AN: 110984Hom.: 34 Cov.: 22 AF XY: 0.0213 AC XY: 708AN XY: 33190
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 20, 2012 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 01, 2013 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at