rs1555970404

Positions:

• chrX-85255275-T-TA

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_Strong PM2 PP5_Very_Strong

The NM_001330574.2(ZNF711):​c.97dup​(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
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2
• Conservation: PhyloP100: 4.41

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]

ACMG classification

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/exons	MANE	Protein	UniProt
ZNF711	NM_001330574.2	c.97dup	p.Thr33AsnfsTer15	frameshift_variant	5/11	ENST00000674551.1	NP_001317503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF711	ENST00000674551.1	c.97dup	p.Thr33AsnfsTer15	frameshift_variant	5/11		NM_001330574.2	ENSP00000502839	P1
ZNF711	ENST00000276123.7	c.97dup	p.Thr33AsnfsTer15	frameshift_variant	5/10	1		ENSP00000276123
ZNF711	ENST00000360700.4	c.97dup	p.Thr33AsnfsTer15	frameshift_variant	4/10	1		ENSP00000353922	P1
ZNF711	ENST00000373165.7	c.97dup	p.Thr33AsnfsTer15	frameshift_variant	4/9	1		ENSP00000362260

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

Submissions by phenotype

Intellectual disability, X-linked 97 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing;provider interpretation

Geisinger Autism and Developmental Medicine Institute, Geisinger Health System

Sep 25, 2017

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

Pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Sep 24, 2019

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

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

Other links and lift over

dbSNP: rs1555970404; hg19: chrX-84510281;