X-85247588-G-A

Variant names:

• chrX-85247588-G-A
• NM_001330574.2:c.16G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330574.2(ZNF711):​c.16G>A​(p.Gly6Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. G6V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF711 NM_001330574.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.00
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38975954).

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.16G>A	p.Gly6Arg	missense	Exon 4 of 11	NP_001317503.1	Q9Y462-3
	ZNF711	NM_001375431.1		c.16G>A	p.Gly6Arg	missense	Exon 2 of 9	NP_001362360.1	Q9Y462-3
	ZNF711	NM_001375432.1		c.16G>A	p.Gly6Arg	missense	Exon 4 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.16G>A	p.Gly6Arg	missense	Exon 4 of 11	ENSP00000502839.1	Q9Y462-3
	ZNF711	ENST00000360700.4	TSL:1	c.16G>A	p.Gly6Arg	missense	Exon 3 of 10	ENSP00000353922.4	Q9Y462-3
	ZNF711	ENST00000276123.7	TSL:1	c.16G>A	p.Gly6Arg	missense	Exon 4 of 10	ENSP00000276123.3	Q9Y462-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.031	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.0
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.25
Sift	Benign	0.16	T
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.19		Loss of catalytic residue at D2 (P = 0.027)
MVP		0.26
MPC		0.79
ClinPred		0.88	D
GERP RS		4.6
Varity_R		0.30
gMVP		0.61
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chrX-84502594;