X-85255758-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability, X-linked 97
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ZNF711 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 212692.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330574.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZNF711	NM_001330574.2	MANE Select	c.579T>G	p.Asp193Glu	missense	Exon 5 of 11	NP_001317503.1
ZNF711	NM_001375431.1		c.579T>G	p.Asp193Glu	missense	Exon 3 of 9	NP_001362360.1
ZNF711	NM_001375432.1		c.579T>G	p.Asp193Glu	missense	Exon 5 of 11	NP_001362361.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZNF711	ENST00000674551.1	MANE Select	c.579T>G	p.Asp193Glu	missense	Exon 5 of 11	ENSP00000502839.1
ZNF711	ENST00000360700.4	TSL:1	c.579T>G	p.Asp193Glu	missense	Exon 4 of 10	ENSP00000353922.4
ZNF711	ENST00000276123.7	TSL:1	c.579T>G	p.Asp193Glu	missense	Exon 5 of 10	ENSP00000276123.3

Frequencies

GnomAD3 genomes

AF:

0.0000898

AC:

AN:

111303

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000331

AC:

AN:

181288

AF XY:

0.0000301

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 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

African (AFR)

AF:

0.0000758

AC:

AN:

26399

American (AMR)

AF:

0.00

AC:

AN:

35176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19361

East Asian (EAS)

AF:

0.00

AC:

AN:

30198

South Asian (SAS)

AF:

0.00

AC:

AN:

54074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841980

Other (OTH)

AF:

0.0000868

AC:

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000898

AC:

AN:

111359

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33547

show subpopulations

African (AFR)

AF:

0.000326

AC:

AN:

30662

American (AMR)

AF:

0.00

AC:

AN:

10481

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3539

South Asian (SAS)

AF:

0.00

AC:

AN:

2626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53056

Other (OTH)

AF:

0.00

AC:

AN:

1524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000328

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

May 12, 2015

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

May 09, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.66

M_CAP

Benign

0.0098

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.90

PhyloP100

0.92

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.73

REVEL

Benign

0.095

Sift

Benign

0.15

Sift4G

Benign

0.13

Polyphen

0.39

Vest4

0.088

MutPred

0.44

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

Mutation Taster

=295/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over