X-85246011-A-T

Position:

• chrX-85246011-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001330574.2(ZNF711):​c.-297A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 111,915 control chromosomes in the GnomAD database, including 2 homozygotes. There are 88 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0034 (2 hom., 88 hem., cov: 24)
• Consequence: ZNF711 NM_001330574.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.320

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-85246011-A-T is Benign according to our data. Variant chrX-85246011-A-T is described in ClinVar as [Benign]. Clinvar id is 914804.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF711	NM_001330574.2	c.-297A>T		5_prime_UTR_variant	2/11	ENST00000674551.1	NP_001317503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF711	ENST00000674551.1	c.-297A>T		5_prime_UTR_variant	2/11		NM_001330574.2	ENSP00000502839	P1
ZNF711	ENST00000276123.7	c.-292A>T		5_prime_UTR_variant	2/10	1		ENSP00000276123
ZNF711	ENST00000360700.4	c.-655A>T		5_prime_UTR_variant	2/10	1		ENSP00000353922	P1
ZNF711	ENST00000373165.7	c.-38A>T		5_prime_UTR_variant	2/9	1		ENSP00000362260

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 376 AN: 111862 Hom.: 2 Cov.: 24 AF XY: 0.00258 AC XY: 88 AN XY: 34062

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000849

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: 0.0000565

Gnomad OTH AF: 0.00200

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00336 AC: 376 AN: 111915 Hom.: 2 Cov.: 24 AF XY: 0.00258 AC XY: 88 AN XY: 34125

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.000848

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000565

Gnomad4 OTH AF: 0.00197

Alfa AF: 0.00214 Hom.: 6

Bravo AF: 0.00363

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 97 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs772828408; hg19: chrX-84501017;