Variant rs189835360 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007137.5(ZNF81):c.417A>G(p.Ile139Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,207,614 control chromosomes in the GnomAD database, including 1 homozygotes. There are 77 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 40 hem., cov: 22)

Exomes 𝑓: 0.00015 ( 1 hom. 37 hem. )

Consequence

ZNF81
NM_007137.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.310

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043881834).

BP6

Variant X-47915063-A-G is Benign according to our data. Variant chrX-47915063-A-G is described in ClinVar as [Benign]. Clinvar id is 212697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 40 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF81	NM_007137.5 linkuse as main transcript	c.417A>G	p.Ile139Met	missense_variant	5/5	ENST00000338637.13	NP_009068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF81	ENST00000338637.13 linkuse as main transcript	c.417A>G	p.Ile139Met	missense_variant	5/5	3	NM_007137.5	ENSP00000341151	P1
ZNF81	ENST00000376954.6 linkuse as main transcript	c.417A>G	p.Ile139Met	missense_variant	6/6	5		ENSP00000366153	P1
ZNF81	ENST00000376950.4 linkuse as main transcript	c.277+19123A>G		intron_variant		5		ENSP00000366149

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

155

AN:

111229

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

33421

show subpopulations

Gnomad AFR

AF:

0.00474

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000575

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:

0.0000377

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000331

AC:

AN:

177991

Hom.:

AF XY:

0.000171

AC XY:

AN XY:

64323

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.000411

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:

0.00

Gnomad OTH exome

AF:

0.000458

GnomAD4 exome

AF:

0.000145

AC:

159

AN:

1096334

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

362002

show subpopulations

Gnomad4 AFR exome

AF:

0.00399

Gnomad4 AMR exome

AF:

0.000573

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000561

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000630

GnomAD4 genome

AF:

0.00142

AC:

158

AN:

111280

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

33482

show subpopulations

Gnomad4 AFR

AF:

0.00483

Gnomad4 AMR

AF:

0.000574

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.00182

ESP6500AA

AF:

0.00384

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000373

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 18, 2017

- -

ZNF81-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 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). -

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

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.86

CADD

Benign

9.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.043

T;T

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.27

.;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.079

Sift

Benign

0.12

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.16

B;B

Vest4

0.12

MVP

0.35

MPC

0.16

ClinPred

0.011

GERP RS

-3.0

Varity_R

0.086

gMVP

0.22

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