rs1555970404

Variant names:

• chrX-85255275-T-TA
• rs1555970404
• NM_001330574.2:c.97dupA

Variant summary

Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PVS1_Strong PM2 PP5_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
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2
• Conservation: PhyloP100: 4.41
• Publications: 0 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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

ACMG classification

Our verdict: Pathogenic. The variant received 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. There are 15 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 Pathogenic/Likely_pathogenic. ClinVar VariationId is 450911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF711	NM_001330574.2	MANE Select	c.97dupA	p.Thr33AsnfsTer15	frameshift	Exon 5 of 11	NP_001317503.1	Q9Y462-3
	ZNF711	NM_001375431.1		c.97dupA	p.Thr33AsnfsTer15	frameshift	Exon 3 of 9	NP_001362360.1	Q9Y462-3
	ZNF711	NM_001375432.1		c.97dupA	p.Thr33AsnfsTer15	frameshift	Exon 5 of 11	NP_001362361.1	Q9Y462-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF711	ENST00000674551.1	MANE Select	c.97dupA	p.Thr33AsnfsTer15	frameshift	Exon 5 of 11	ENSP00000502839.1	Q9Y462-3
	ZNF711	ENST00000360700.4	TSL:1	c.97dupA	p.Thr33AsnfsTer15	frameshift	Exon 4 of 10	ENSP00000353922.4	Q9Y462-3
	ZNF711	ENST00000276123.7	TSL:1	c.97dupA	p.Thr33AsnfsTer15	frameshift	Exon 5 of 10	ENSP00000276123.3	Q9Y462-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Pathogenic/Likely pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
1	-	-	Intellectual disability, X-linked 97 (1)
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4
Mutation Taster		=9/191	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1555970404; hg19: chrX-84510281;