Variant X-47915248-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007137.5(ZNF81):c.602A>T(p.His201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000707 in 1,209,621 control chromosomes in the GnomAD database, including 2 homozygotes. There are 259 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., 11 hem., cov: 22)

Exomes 𝑓: 0.00074 ( 1 hom. 248 hem. )

Consequence

ZNF81
NM_007137.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.496

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02247873).

BP6

Variant X-47915248-A-T is Benign according to our data. Variant chrX-47915248-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042874.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF81	NM_007137.5 linkuse as main transcript	c.602A>T	p.His201Leu	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.602A>T	p.His201Leu	missense_variant	5/5	3	NM_007137.5	P1
ZNF81	ENST00000376954.6 linkuse as main transcript	c.602A>T	p.His201Leu	missense_variant	6/6	5		P1
ZNF81	ENST00000376950.4 linkuse as main transcript	c.277+19308A>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000393

AC:

AN:

112073

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

AN XY:

34221

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000950

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:

0.000507

Gnomad OTH

AF:

0.00199

GnomAD3 exomes

AF:

0.000420

AC:

AN:

180750

Hom.:

AF XY:

0.000389

AC XY:

AN XY:

66910

show subpopulations

Gnomad AFR exome

AF:

0.0000808

Gnomad AMR exome

AF:

0.000919

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:

0.000580

Gnomad OTH exome

AF:

0.000678

GnomAD4 exome

AF:

0.000739

AC:

811

AN:

1097495

Hom.:

Cov.:

AF XY:

0.000683

AC XY:

248

AN XY:

363001

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000968

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.000882

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000392

AC:

AN:

112126

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

AN XY:

34284

show subpopulations

Gnomad4 AFR

AF:

0.000129

Gnomad4 AMR

AF:

0.000949

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000507

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.000475

Hom.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000471

AC:

ExAC

AF:

0.000290

AC:

EpiCase

AF:

0.000764

EpiControl

AF:

0.000830

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

Apr 29, 2022

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

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Benign

0.93

DEOGEN2

Benign

0.16

T;T

FATHMM_MKL

Benign

0.20

M_CAP

Benign

0.0028

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.051

Sift

Benign

0.69

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0080

B;B

Vest4

0.15

MVP

0.71

MPC

0.20

ClinPred

0.0093

GERP RS

2.6

Varity_R

0.18

gMVP

0.13

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