rs200890712

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_007137.5(ZNF81):c.1264G>A(p.Ala422Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000919 in 1,208,341 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000091 ( 0 hom. 27 hem. )

Consequence

ZNF81
NM_007137.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.83

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19505426).

BP6

Variant X-47915910-G-A is Benign according to our data. Variant chrX-47915910-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 130852.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF81	NM_007137.5 linkuse as main transcript	c.1264G>A	p.Ala422Thr	missense_variant	5/5	ENST00000338637.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF81	ENST00000338637.13 linkuse as main transcript	c.1264G>A	p.Ala422Thr	missense_variant	5/5	3	NM_007137.5	P1
ZNF81	ENST00000376954.6 linkuse as main transcript	c.1264G>A	p.Ala422Thr	missense_variant	6/6	5		P1
ZNF81	ENST00000376950.4 linkuse as main transcript	c.277+19970G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000989

AC:

AN:

111213

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

33415

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000444

AC:

AN:

180038

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

65676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000995

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000911

AC:

100

AN:

1097128

Hom.:

Cov.:

AF XY:

0.0000745

AC XY:

AN XY:

362656

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000989

AC:

AN:

111213

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

33415

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000208

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	ZNF81: BS2 -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 12, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T

FATHMM_MKL

Benign

0.042

M_CAP

Benign

0.045

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.65

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.14

Sift

Benign

0.34

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.57

P;P

Vest4

0.13

MVP

0.59

MPC

0.65

ClinPred

0.14

GERP RS

4.1

Varity_R

0.27

gMVP

0.042

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.

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