rs1471128641

Variant names:

• chrX-85270741-G-A
• rs1471128641
• NM_001330574.2:c.1337G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001330574.2(ZNF711):​c.1337G>A​(p.Arg446Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,203,451 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 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: 22)
  • Exomes 𝑓: 0.000048 (0 hom. 17 hem.)
• Consequence: ZNF711 NM_001330574.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.19
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32750845).
• BS2: High Hemizygotes in GnomAdExome4 at 17 XL gene

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.1337G>A	p.Arg446Lys	missense	Exon 11 of 11	NP_001317503.1	Q9Y462-3
	ZNF711	NM_001375431.1		c.1337G>A	p.Arg446Lys	missense	Exon 9 of 9	NP_001362360.1	Q9Y462-3
	ZNF711	NM_001375432.1		c.1337G>A	p.Arg446Lys	missense	Exon 11 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.1337G>A	p.Arg446Lys	missense	Exon 11 of 11	ENSP00000502839.1	Q9Y462-3
	ZNF711	ENST00000360700.4	TSL:1	c.1337G>A	p.Arg446Lys	missense	Exon 10 of 10	ENSP00000353922.4	Q9Y462-3
	ZNF711	ENST00000276123.7	TSL:1	c.1199G>A	p.Arg400Lys	missense	Exon 10 of 10	ENSP00000276123.3	Q9Y462-1

Frequencies

GnomAD3 genomes AF: 0.00000900 AC: 1 AN: 111068 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000116 AC: 2 AN: 171685 AF XY: 0.0000173

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000649

Gnomad NFE exome AF: 0.0000134

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000476 AC: 52 AN: 1092383 Hom.: 0 Cov.: 30 AF XY: 0.0000474 AC XY: 17 AN XY: 358615

African (AFR) AF: 0.00 AC: 0 AN: 26294

American (AMR) AF: 0.00 AC: 0 AN: 34814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19290

East Asian (EAS) AF: 0.00 AC: 0 AN: 30034

South Asian (SAS) AF: 0.00 AC: 0 AN: 53254

European-Finnish (FIN) AF: 0.0000248 AC: 1 AN: 40270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4106

European-Non Finnish (NFE) AF: 0.0000596 AC: 50 AN: 838486

Other (OTH) AF: 0.0000218 AC: 1 AN: 45835

GnomAD4 genome AF: 0.00000900 AC: 1 AN: 111068 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33382

African (AFR) AF: 0.00 AC: 0 AN: 30588

American (AMR) AF: 0.00 AC: 0 AN: 10362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3514

South Asian (SAS) AF: 0.00 AC: 0 AN: 2642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52920

Other (OTH) AF: 0.00 AC: 0 AN: 1499

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	N
PhyloP100		8.2
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.15	T
Sift4G	Benign	0.27	T
Polyphen		0.068	B
Vest4		0.27
MutPred		0.57		Gain of methylation at R400 (P = 0.0335)
MVP		0.39
MPC		1.5
ClinPred		0.35	T
GERP RS		5.5
Varity_R		0.41
gMVP		0.51
Mutation Taster		=63/37	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: rs1471128641; hg19: chrX-84525747;