chrX-85271431-G-A

Variant names:

• chrX-85271431-G-A
• rs201449359
• NM_001330574.2:c.2027G>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.2027G>A​(p.Arg676His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,209,232 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: ZNF711 NM_001330574.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.99
• 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: 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31920445).

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.2027G>A	p.Arg676His	missense	Exon 11 of 11	NP_001317503.1
	ZNF711	NM_001375431.1		c.2027G>A	p.Arg676His	missense	Exon 9 of 9	NP_001362360.1
	ZNF711	NM_001375432.1		c.2027G>A	p.Arg676His	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.2027G>A	p.Arg676His	missense	Exon 11 of 11	ENSP00000502839.1
	ZNF711	ENST00000360700.4	TSL:1	c.2027G>A	p.Arg676His	missense	Exon 10 of 10	ENSP00000353922.4
	ZNF711	ENST00000276123.7	TSL:1	c.1889G>A	p.Arg630His	missense	Exon 10 of 10	ENSP00000276123.3

Frequencies

GnomAD3 genomes AF: 0.00000898 AC: 1 AN: 111417 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000287

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000547 AC: 1 AN: 182662 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000723

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097763 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363379

African (AFR) AF: 0.0000379 AC: 1 AN: 26376

American (AMR) AF: 0.00 AC: 0 AN: 35115

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19368

East Asian (EAS) AF: 0.00 AC: 0 AN: 30187

South Asian (SAS) AF: 0.00 AC: 0 AN: 54135

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40505

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841894

Other (OTH) AF: 0.00 AC: 0 AN: 46052

GnomAD4 genome AF: 0.00000897 AC: 1 AN: 111469 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33753

African (AFR) AF: 0.00 AC: 0 AN: 30721

American (AMR) AF: 0.00 AC: 0 AN: 10501

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.000288 AC: 1 AN: 3474

South Asian (SAS) AF: 0.00 AC: 0 AN: 2621

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6067

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53025

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Apr 14, 2017

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		8.0
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.43
Sift	Benign	0.037	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.55		Loss of phosphorylation at S632 (P = 0.0694)
MVP		0.37
MPC		1.6
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.33
gMVP		0.52
Mutation Taster		=57/43	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: rs201449359; hg19: chrX-84526437;