X-85246011-A-T

Variant names:

• chrX-85246011-A-T
• rs772828408
• NM_001330574.2:c.-297A>T

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 VariationId is 914804.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 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.-297A>T		5_prime_UTR	Exon 2 of 11	NP_001317503.1	Q9Y462-3
	ZNF711	NM_001375432.1		c.-292A>T		5_prime_UTR	Exon 2 of 11	NP_001362361.1	Q9Y462-3
	ZNF711	NM_001375433.1		c.-655A>T		5_prime_UTR	Exon 2 of 10	NP_001362362.1	Q9Y462-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF711	ENST00000674551.1	MANE Select	c.-297A>T		5_prime_UTR	Exon 2 of 11	ENSP00000502839.1	Q9Y462-3
	ZNF711	ENST00000360700.4	TSL:1	c.-655A>T		5_prime_UTR	Exon 2 of 10	ENSP00000353922.4	Q9Y462-3
	ZNF711	ENST00000276123.7	TSL:1	c.-292A>T		5_prime_UTR	Exon 2 of 10	ENSP00000276123.3	Q9Y462-1

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 376 AN: 111862 Hom.: 2 Cov.: 24

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

African (AFR) AF: 0.0117 AC: 361 AN: 30820

American (AMR) AF: 0.000848 AC: 9 AN: 10612

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3583

South Asian (SAS) AF: 0.00 AC: 0 AN: 2670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6071

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

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53091

Other (OTH) AF: 0.00197 AC: 3 AN: 1520

Alfa AF: 0.00214 Hom.: 6

Bravo AF: 0.00363

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual disability, X-linked 97 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.74
PhyloP100		0.32
Mutation Taster		=299/1	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: rs772828408; hg19: chrX-84501017;