rs145361311

Positions:

chrX-85265168-G-A

Variant summary

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

The NM_001330574.2(ZNF711):c.829G>A(p.Ala277Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,205,732 control chromosomes in the GnomAD database, including 1 homozygotes. There are 71 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 0.0011 ( 1 hom., 36 hem., cov: 22)

Exomes 𝑓: 0.00011 ( 0 hom. 35 hem. )

Consequence

ZNF711
NM_001330574.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.20

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009436458).

BP6

Variant X-85265168-G-A is Benign according to our data. Variant chrX-85265168-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 36 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF711	NM_001330574.2 linkuse as main transcript	c.829G>A	p.Ala277Thr	missense_variant	7/11	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.829G>A	p.Ala277Thr	missense_variant	7/11		NM_001330574.2	ENSP00000502839.1	Q9Y462-3
ZNF711	ENST00000360700.4 linkuse as main transcript	c.829G>A	p.Ala277Thr	missense_variant	6/10	1		ENSP00000353922.4	Q9Y462-3
ZNF711	ENST00000276123.7 linkuse as main transcript	c.829G>A	p.Ala277Thr	missense_variant	7/10	1		ENSP00000276123.3	Q9Y462-1
ZNF711	ENST00000373165.7 linkuse as main transcript	c.829G>A	p.Ala277Thr	missense_variant	6/9	1		ENSP00000362260.3	Q9Y462-1

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

122

AN:

110685

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

32967

show subpopulations

Gnomad AFR

AF:

0.00387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000291

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:

0.000675

GnomAD3 exomes

AF:

0.000371

AC:

AN:

183060

Hom.:

AF XY:

0.000310

AC XY:

AN XY:

67672

show subpopulations

Gnomad AFR exome

AF:

0.00457

Gnomad AMR exome

AF:

0.000293

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:

0.000107

AC:

117

AN:

1094998

Hom.:

Cov.:

AF XY:

0.0000969

AC XY:

AN XY:

361126

show subpopulations

Gnomad4 AFR exome

AF:

0.00380

Gnomad4 AMR exome

AF:

0.000199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.00111

AC:

123

AN:

110734

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

33026

show subpopulations

Gnomad4 AFR

AF:

0.00390

Gnomad4 AMR

AF:

0.000291

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:

0.000667

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.00139

ESP6500AA

AF:

0.00495

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000404

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 24, 2018

- -

See cases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Dec 30, 2021

ACMG classification criteria: BS1, BS2, BP4 -

Intellectual disability, X-linked 97

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

T;T;.

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.76

.;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.0094

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.62

N;N;N

REVEL

Benign

0.027

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.0050

B;B;B

Vest4

0.14

MVP

0.28

MPC

1.2

ClinPred

0.021

GERP RS

-0.14

Varity_R

0.077

gMVP

0.43

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