X-85246027-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001330574.2(ZNF711):c.-286+5C>T variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 111,010 control chromosomes in the GnomAD database, including 2,464 homozygotes. There are 6,801 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (2464 hom., 6801 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: ZNF711 NM_001330574.2 splice_donor_5th_base, intron
• Scores: Splicing: ADA: 0.00001267
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.716

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant X-85246027-C-T is Benign according to our data. Variant chrX-85246027-C-T is described in ClinVar as [Benign]. Clinvar id is 130847.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-85246027-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF711	NM_001330574.2	c.-286+5C>T		splice_donor_5th_base_variant, intron_variant		ENST00000674551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF711	ENST00000674551.1	c.-286+5C>T		splice_donor_5th_base_variant, intron_variant			NM_001330574.2	P1
ZNF711	ENST00000276123.7	c.-281+5C>T		splice_donor_5th_base_variant, intron_variant		1
ZNF711	ENST00000360700.4	c.-644+5C>T		splice_donor_5th_base_variant, intron_variant		1		P1
ZNF711	ENST00000373165.7	c.-27+5C>T		splice_donor_5th_base_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 23959 AN: 110958 Hom.: 2466 Cov.: 23 AF XY: 0.203 AC XY: 6761 AN XY: 33226

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.0426

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.185

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.216 AC: 24003 AN: 111010 Hom.: 2464 Cov.: 23 AF XY: 0.204 AC XY: 6801 AN XY: 33288

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.185

Alfa AF: 0.190 Hom.: 1100

Bravo AF: 0.219

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

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	-0.64
Cadd	Benign	9.3
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000013
dbscSNV1_RF	Benign	0.0020
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: rs41311563; hg19: chrX-84501033;