chrX-47888073-A-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_007137.5(ZNF81):āc.129A>Gā(p.Arg43=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,208,415 control chromosomes in the GnomAD database, including 11 homozygotes. There are 367 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0063 ( 6 hom., 164 hem., cov: 22)
Exomes š: 0.00068 ( 5 hom. 203 hem. )
Consequence
ZNF81
NM_007137.5 synonymous
NM_007137.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.785
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=-0.91).
BP6
Variant X-47888073-A-G is Benign according to our data. Variant chrX-47888073-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 590232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.785 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00625 (691/110551) while in subpopulation AFR AF= 0.0218 (662/30363). AF 95% confidence interval is 0.0204. There are 6 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF81 | NM_007137.5 | c.129A>G | p.Arg43= | synonymous_variant | 3/5 | ENST00000338637.13 | NP_009068.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF81 | ENST00000338637.13 | c.129A>G | p.Arg43= | synonymous_variant | 3/5 | 3 | NM_007137.5 | ENSP00000341151 | P1 | |
ZNF81 | ENST00000334937.8 | c.129A>G | p.Arg43= | synonymous_variant | 4/4 | 1 | ENSP00000334641 | |||
ZNF81 | ENST00000376954.6 | c.129A>G | p.Arg43= | synonymous_variant | 4/6 | 5 | ENSP00000366153 | P1 | ||
ZNF81 | ENST00000376950.4 | c.129A>G | p.Arg43= | synonymous_variant | 3/5 | 5 | ENSP00000366149 |
Frequencies
GnomAD3 genomes AF: 0.00624 AC: 690AN: 110502Hom.: 6 Cov.: 22 AF XY: 0.00501 AC XY: 164AN XY: 32720
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GnomAD3 exomes AF: 0.00189 AC: 345AN: 182310Hom.: 3 AF XY: 0.00107 AC XY: 72AN XY: 67048
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GnomAD4 exome AF: 0.000676 AC: 742AN: 1097864Hom.: 5 Cov.: 31 AF XY: 0.000559 AC XY: 203AN XY: 363258
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GnomAD4 genome AF: 0.00625 AC: 691AN: 110551Hom.: 6 Cov.: 22 AF XY: 0.00500 AC XY: 164AN XY: 32779
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
ZNF81-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
History of neurodevelopmental disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 15, 2013 | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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