X-85255275-T-TA

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong

The NM_001330574.2(ZNF711):​c.97dupA​(p.Thr33AsnfsTer15) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Genomes: not found (cov: 23)

Consequence

ZNF711
NM_001330574.2 frameshift

Scores

Not classified

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 4.41
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 14 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.96 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-85255275-T-TA is Pathogenic according to our data. Variant chrX-85255275-T-TA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 450911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF711NM_001330574.2 linkc.97dupA p.Thr33AsnfsTer15 frameshift_variant Exon 5 of 11 ENST00000674551.1 NP_001317503.1 Q9Y462-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF711ENST00000674551.1 linkc.97dupA p.Thr33AsnfsTer15 frameshift_variant Exon 5 of 11 NM_001330574.2 ENSP00000502839.1 Q9Y462-3
ZNF711ENST00000360700.4 linkc.97dupA p.Thr33AsnfsTer15 frameshift_variant Exon 4 of 10 1 ENSP00000353922.4 Q9Y462-3
ZNF711ENST00000276123.7 linkc.97dupA p.Thr33AsnfsTer15 frameshift_variant Exon 5 of 10 1 ENSP00000276123.3 Q9Y462-1
ZNF711ENST00000373165.7 linkc.97dupA p.Thr33AsnfsTer15 frameshift_variant Exon 4 of 9 1 ENSP00000362260.3 Q9Y462-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Intellectual disability, X-linked 97 Pathogenic:1
Sep 25, 2017
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing;provider interpretation

This 16 year old male with moderate intellectual disability, obsessive compulsive behaviors, and growth failure was found to carry a de novo variant in the ZNF711 gene. He is non-dysmorphic, in the 2nd percentile for weight, and in the 7th percentile for height. Pathogenic variants in this gene, including truncating variants, are associated with mild to moderate intellectual disability. Mild dysmorphic features and obesity have been reported in other individuals with pathogenic variants in this gene. The variant is absent from population databases and has not been reported previously in affected individuals, to our knowledge. This variant causes a frameshift and is predicted to cause loss of normal protein function. -

not provided Pathogenic:1
Sep 24, 2019
GeneDx
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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.

Other links and lift over

dbSNP: rs1555970404; hg19: chrX-84510281; API