Variant X-85255500-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330574.2(ZNF711):c.321T>A(p.Asp107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,210,045 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D107G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

ZNF711
NM_001330574.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16430691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF711	NM_001330574.2 linkuse as main transcript	c.321T>A	p.Asp107Glu	missense_variant	5/11	ENST00000674551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF711	ENST00000674551.1 linkuse as main transcript	c.321T>A	p.Asp107Glu	missense_variant	5/11		NM_001330574.2	P1	Q9Y462-3
ZNF711	ENST00000360700.4 linkuse as main transcript	c.321T>A	p.Asp107Glu	missense_variant	4/10	1		P1	Q9Y462-3
ZNF711	ENST00000276123.7 linkuse as main transcript	c.321T>A	p.Asp107Glu	missense_variant	5/10	1			Q9Y462-1
ZNF711	ENST00000373165.7 linkuse as main transcript	c.321T>A	p.Asp107Glu	missense_variant	4/9	1			Q9Y462-1

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111806

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33992

show subpopulations

Gnomad AFR

AF:

0.0000326

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

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1098239

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363599

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

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:

0.00

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111806

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33992

show subpopulations

Gnomad4 AFR

AF:

0.0000326

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, X-linked 97

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Oct 06, 2021

ACMG classification criteria: PM2 moderate, BP4 supporting -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T;.

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.0063

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

0.58

N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.64

N;N;N

REVEL

Benign

0.099

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.60

P;P;P

Vest4

0.28

MutPred

0.59

Loss of stability (P = 0.092);Loss of stability (P = 0.092);Loss of stability (P = 0.092);

MVP

0.32

MPC

0.70

ClinPred

0.48

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.33

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