Variant X-47846285-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007137.5(ZNF81):c.18C>T(p.Asp6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0099 in 1,207,438 control chromosomes in the GnomAD database, including 529 homozygotes. There are 3,971 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 80 hom., 527 hem., cov: 23)

Exomes 𝑓: 0.0095 ( 449 hom. 3444 hem. )

Consequence

ZNF81
NM_007137.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.680

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]

ZNF81 links:

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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=-0.75).

BP6

Variant X-47846285-C-T is Benign according to our data. Variant chrX-47846285-C-T is described in ClinVar as [Benign]. Clinvar id is 130853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47846285-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF81	NM_007137.5 linkuse as main transcript	c.18C>T	p.Asp6=	synonymous_variant	2/5	ENST00000338637.13	NP_009068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF81	ENST00000338637.13 linkuse as main transcript	c.18C>T	p.Asp6=	synonymous_variant	2/5	3	NM_007137.5	ENSP00000341151	P1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

1571

AN:

112152

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

527

AN XY:

34308

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0699

Gnomad ASJ

AF:

0.00265

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.0446

Gnomad FIN

AF:

0.000163

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000375

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.0310

AC:

5397

AN:

173823

Hom.:

247

AF XY:

0.0261

AC XY:

1592

AN XY:

60901

show subpopulations

Gnomad AFR exome

AF:

0.00261

Gnomad AMR exome

AF:

0.0939

Gnomad ASJ exome

AF:

0.00315

Gnomad EAS exome

AF:

0.162

Gnomad SAS exome

AF:

0.0328

Gnomad FIN exome

AF:

0.0000670

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.0236

GnomAD4 exome

AF:

0.00948

AC:

10382

AN:

1095232

Hom.:

449

Cov.:

AF XY:

0.00953

AC XY:

3444

AN XY:

361240

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.0929

Gnomad4 ASJ exome

AF:

0.00238

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.0311

Gnomad4 FIN exome

AF:

0.0000248

Gnomad4 NFE exome

AF:

0.000307

Gnomad4 OTH exome

AF:

0.0195

GnomAD4 genome

AF:

0.0140

AC:

1567

AN:

112206

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

527

AN XY:

34372

show subpopulations

Gnomad4 AFR

AF:

0.00204

Gnomad4 AMR

AF:

0.0701

Gnomad4 ASJ

AF:

0.00265

Gnomad4 EAS

AF:

0.163

Gnomad4 SAS

AF:

0.0436

Gnomad4 FIN

AF:

0.000163

Gnomad4 NFE

AF:

0.000376

Gnomad4 OTH

AF:

0.0262

Alfa

AF:

0.00463

Hom.:

Bravo

AF:

0.0200

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	Ambry Genetics	Nov 24, 2014	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 07, 2013	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.7

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over