X-85270872-A-G

Variant names:

• chrX-85270872-A-G
• rs772353719
• NM_001330574.2:c.1468A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330574.2(ZNF711):​c.1468A>G​(p.Lys490Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K490Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF711 NM_001330574.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.73
• Publications: 1 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14638337).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF711	NM_001330574.2	MANE Select	c.1468A>G	p.Lys490Glu	missense	Exon 11 of 11	NP_001317503.1
	ZNF711	NM_001375431.1		c.1468A>G	p.Lys490Glu	missense	Exon 9 of 9	NP_001362360.1
	ZNF711	NM_001375432.1		c.1468A>G	p.Lys490Glu	missense	Exon 11 of 11	NP_001362361.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF711	ENST00000674551.1	MANE Select	c.1468A>G	p.Lys490Glu	missense	Exon 11 of 11	ENSP00000502839.1
	ZNF711	ENST00000360700.4	TSL:1	c.1468A>G	p.Lys490Glu	missense	Exon 10 of 10	ENSP00000353922.4
	ZNF711	ENST00000276123.7	TSL:1	c.1330A>G	p.Lys444Glu	missense	Exon 10 of 10	ENSP00000276123.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.39	B
Vest4		0.41
MutPred		0.45		Loss of methylation at K444 (P = 9e-04)
MVP		0.34
MPC		1.7
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.53
gMVP		0.55
Mutation Taster		=96/4	polymorphism

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: rs772353719; hg19: chrX-84525878;