chrX-85246027-C-T

Variant names:

• chrX-85246027-C-T
• rs41311563
• NM_001330574.2:c.-286+5C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001330574.2(ZNF711):​c.-286+5C>T variant causes a splice region, 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_region, intron
• Scores: Splicing: ADA: 0.00001267
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.716
• 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: 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: Benign. The variant received -20 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 VariationId is 130847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

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.-286+5C>T		splice_region intron	N/A	NP_001317503.1	Q9Y462-3
	ZNF711	NM_001375431.1		c.-26-1520C>T		intron	N/A	NP_001362360.1	Q9Y462-3
	ZNF711	NM_001375432.1		c.-281+5C>T		splice_region intron	N/A	NP_001362361.1	Q9Y462-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF711	ENST00000674551.1	MANE Select	c.-286+5C>T		splice_region intron	N/A	ENSP00000502839.1	Q9Y462-3
	ZNF711	ENST00000360700.4	TSL:1	c.-644+5C>T		splice_region intron	N/A	ENSP00000353922.4	Q9Y462-3
	ZNF711	ENST00000276123.7	TSL:1	c.-281+5C>T		splice_region intron	N/A	ENSP00000276123.3	Q9Y462-1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 23959 AN: 110958 Hom.: 2466 Cov.: 23

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.403 AC: 12260 AN: 30437

American (AMR) AF: 0.154 AC: 1623 AN: 10539

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 476 AN: 2641

East Asian (EAS) AF: 0.152 AC: 535 AN: 3528

South Asian (SAS) AF: 0.199 AC: 532 AN: 2667

European-Finnish (FIN) AF: 0.161 AC: 947 AN: 5886

Middle Eastern (MID) AF: 0.134 AC: 29 AN: 216

European-Non Finnish (NFE) AF: 0.138 AC: 7293 AN: 52909

Other (OTH) AF: 0.185 AC: 279 AN: 1507

Alfa AF: 0.190 Hom.: 1100

Bravo AF: 0.219

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual disability, X-linked 97 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.3
DANN	Benign	0.49
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41311563; hg19: chrX-84501033;