chrX-47888073-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_007137.5(ZNF81):ā€‹c.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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.785
Variant links:
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
ZNF81NM_007137.5 linkuse as main transcriptc.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
ZNF81ENST00000338637.13 linkuse as main transcriptc.129A>G p.Arg43= synonymous_variant 3/53 NM_007137.5 ENSP00000341151 P1
ZNF81ENST00000334937.8 linkuse as main transcriptc.129A>G p.Arg43= synonymous_variant 4/41 ENSP00000334641
ZNF81ENST00000376954.6 linkuse as main transcriptc.129A>G p.Arg43= synonymous_variant 4/65 ENSP00000366153 P1
ZNF81ENST00000376950.4 linkuse as main transcriptc.129A>G p.Arg43= synonymous_variant 3/55 ENSP00000366149

Frequencies

GnomAD3 genomes
AF:
0.00624
AC:
690
AN:
110502
Hom.:
6
Cov.:
22
AF XY:
0.00501
AC XY:
164
AN XY:
32720
show subpopulations
Gnomad AFR
AF:
0.0218
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00222
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:
0.00
Gnomad OTH
AF:
0.00405
GnomAD3 exomes
AF:
0.00189
AC:
345
AN:
182310
Hom.:
3
AF XY:
0.00107
AC XY:
72
AN XY:
67048
show subpopulations
Gnomad AFR exome
AF:
0.0232
Gnomad AMR exome
AF:
0.00150
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000369
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000676
AC:
742
AN:
1097864
Hom.:
5
Cov.:
31
AF XY:
0.000559
AC XY:
203
AN XY:
363258
show subpopulations
Gnomad4 AFR exome
AF:
0.0227
Gnomad4 AMR exome
AF:
0.00179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000190
Gnomad4 OTH exome
AF:
0.00135
GnomAD4 genome
AF:
0.00625
AC:
691
AN:
110551
Hom.:
6
Cov.:
22
AF XY:
0.00500
AC XY:
164
AN XY:
32779
show subpopulations
Gnomad4 AFR
AF:
0.0218
Gnomad4 AMR
AF:
0.00221
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00400
Alfa
AF:
0.00330
Hom.:
14
Bravo
AF:
0.00739

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 providedclinical testingPreventionGenetics, part of Exact SciencesMar 25, 2019This 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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
History of neurodevelopmental disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMar 15, 2013This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
6.5
DANN
Benign
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148626389; hg19: chrX-47747472; API