Variant X-47888091-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007137.5(ZNF81):c.147A>G(p.Val49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,208,069 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 75 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00014 ( 0 hom. 73 hem. )

Consequence

ZNF81
NM_007137.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.126

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-47888091-A-G is Benign according to our data. Variant chrX-47888091-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3047681.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.126 with no splicing effect.

BS2

High Hemizygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF81	NM_007137.5 linkuse as main transcript	c.147A>G	p.Val49=	synonymous_variant	3/5	ENST00000338637.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF81	ENST00000338637.13 linkuse as main transcript	c.147A>G	p.Val49=	synonymous_variant	3/5	3	NM_007137.5	P1
ZNF81	ENST00000334937.8 linkuse as main transcript	c.147A>G	p.Val49=	synonymous_variant	4/4	1
ZNF81	ENST00000376954.6 linkuse as main transcript	c.147A>G	p.Val49=	synonymous_variant	4/6	5		P1
ZNF81	ENST00000376950.4 linkuse as main transcript	c.147A>G	p.Val49=	synonymous_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.0000904

AC:

AN:

110622

Hom.:

Cov.:

AF XY:

0.0000609

AC XY:

AN XY:

32822

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00350

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00429

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000310

AC:

AN:

180747

Hom.:

AF XY:

0.000381

AC XY:

AN XY:

65635

show subpopulations

Gnomad AFR exome

AF:

0.0000777

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00283

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000451

GnomAD4 exome

AF:

0.000137

AC:

150

AN:

1097397

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

362815

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.0000904

AC:

AN:

110672

Hom.:

Cov.:

AF XY:

0.0000608

AC XY:

AN XY:

32882

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00351

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZNF81-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

Cadd

Benign

6.1

Dann

Benign

0.56

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