chrX-85255758-T-G

Position:

chrX-85255758-T-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001330574.2(ZNF711):c.579T>G(p.Asp193Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,209,074 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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 0.000090 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.0000055 ( 0 hom. 1 hem. )

Consequence

ZNF711
NM_001330574.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.921

Variant links:

Genes affected

ZNF711 (HGNC:13128): (zinc finger protein 711) This gene encodes a zinc finger protein of unknown function. It bears similarity to a zinc finger protein which acts as a transcriptional activator. This gene lies in a region of the X chromosome which has been associated with cognitive disability. [provided by RefSeq, Jul 2008]

ZNF711 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025405496).

BP6

Variant X-85255758-T-G is Benign according to our data. Variant chrX-85255758-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212692.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF711	NM_001330574.2 linkuse as main transcript	c.579T>G	p.Asp193Glu	missense_variant	5/11	ENST00000674551.1	NP_001317503.1	Q9Y462-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF711	ENST00000674551.1 linkuse as main transcript	c.579T>G	p.Asp193Glu	missense_variant	5/11		NM_001330574.2	ENSP00000502839.1	Q9Y462-3
ZNF711	ENST00000360700.4 linkuse as main transcript	c.579T>G	p.Asp193Glu	missense_variant	4/10	1		ENSP00000353922.4	Q9Y462-3
ZNF711	ENST00000276123.7 linkuse as main transcript	c.579T>G	p.Asp193Glu	missense_variant	5/10	1		ENSP00000276123.3	Q9Y462-1
ZNF711	ENST00000373165.7 linkuse as main transcript	c.579T>G	p.Asp193Glu	missense_variant	4/9	1		ENSP00000362260.3	Q9Y462-1

Frequencies

GnomAD3 genomes

AF:

0.0000898

AC:

AN:

111303

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33481

show subpopulations

Gnomad AFR

AF:

0.000327

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000331

AC:

AN:

181288

Hom.:

AF XY:

0.0000301

AC XY:

AN XY:

66514

show subpopulations

Gnomad AFR exome

AF:

0.000468

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1097715

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363117

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

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:

0.00

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.0000898

AC:

AN:

111359

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33547

show subpopulations

Gnomad4 AFR

AF:

0.000326

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000593

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 12, 2015

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

This alteration is classified as likely 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;T;.

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.66

.;T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.73

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.39

B;B;D

Vest4

0.088

MutPred

0.44

Gain of glycosylation at T188 (P = 0.1501);Gain of glycosylation at T188 (P = 0.1501);Gain of glycosylation at T188 (P = 0.1501);

MVP

0.37

MPC

1.3

ClinPred

0.14

GERP RS

-2.3

Varity_R

0.10

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