rs587780528

Variant names:

• chrX-85255300-ATTG-A
• rs587780527
• NM_001330574.2:c.127_129delGTT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001330574.2(ZNF711):​c.127_129delGTT​(p.Val43del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,980 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ZNF711 NM_001330574.2 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 O:1
• Conservation: PhyloP100: 7.37
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001330574.2. Strenght limited to Supporting due to length of the change: 1aa.

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.127_129delGTT	p.Val43del	conservative_inframe_deletion	Exon 5 of 11	NP_001317503.1	Q9Y462-3
	ZNF711	NM_001375431.1		c.127_129delGTT	p.Val43del	conservative_inframe_deletion	Exon 3 of 9	NP_001362360.1	Q9Y462-3
	ZNF711	NM_001375432.1		c.127_129delGTT	p.Val43del	conservative_inframe_deletion	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.127_129delGTT	p.Val43del	conservative_inframe_deletion	Exon 5 of 11	ENSP00000502839.1	Q9Y462-3
	ZNF711	ENST00000360700.4	TSL:1	c.127_129delGTT	p.Val43del	conservative_inframe_deletion	Exon 4 of 10	ENSP00000353922.4	Q9Y462-3
	ZNF711	ENST00000276123.7	TSL:1	c.127_129delGTT	p.Val43del	conservative_inframe_deletion	Exon 5 of 10	ENSP00000276123.3	Q9Y462-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097980 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 363340

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26396

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19380

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841900

Other (OTH) AF: 0.00 AC: 0 AN: 46087

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	-	-	Intellectual disability, X-linked 97 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

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

Other links and lift over

dbSNP: rs587780527; hg19: chrX-84510306;