NM_001330574.2:c.79+6G>A

Variant names:

• chrX-85247657-G-A
• rs373653025
• NM_001330574.2:c.79+6G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001330574.2(ZNF711):​c.79+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000866 in 1,200,815 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000091 (0 hom. 39 hem.)
• Consequence: ZNF711 NM_001330574.2 splice_region, intron
• Scores: Splicing: ADA: 0.006646
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.216
• 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant X-85247657-G-A is Benign according to our data. Variant chrX-85247657-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661002.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 39 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF711	NM_001330574.2	c.79+6G>A		splice_region_variant, intron_variant	Intron 4 of 10	ENST00000674551.1	NP_001317503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF711	ENST00000674551.1	c.79+6G>A		splice_region_variant, intron_variant	Intron 4 of 10		NM_001330574.2	ENSP00000502839.1
ZNF711	ENST00000360700.4	c.79+6G>A		splice_region_variant, intron_variant	Intron 3 of 9	1		ENSP00000353922.4
ZNF711	ENST00000276123.7	c.79+6G>A		splice_region_variant, intron_variant	Intron 4 of 9	1		ENSP00000276123.3
ZNF711	ENST00000373165.7	c.79+6G>A		splice_region_variant, intron_variant	Intron 3 of 8	1		ENSP00000362260.3

Frequencies

GnomAD3 genomes AF: 0.0000446 AC: 5 AN: 112073 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: 0.000825

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000284 AC: 52 AN: 183174 AF XY: 0.000251

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: 0.00119

Gnomad NFE exome AF: 0.000379

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000909 AC: 99 AN: 1088742 Hom.: 0 Cov.: 27 AF XY: 0.000110 AC XY: 39 AN XY: 354472

African (AFR) AF: 0.00 AC: 0 AN: 26241

American (AMR) AF: 0.00 AC: 0 AN: 35191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19314

East Asian (EAS) AF: 0.00 AC: 0 AN: 30150

South Asian (SAS) AF: 0.000130 AC: 7 AN: 53849

European-Finnish (FIN) AF: 0.000841 AC: 34 AN: 40435

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.0000540 AC: 45 AN: 833647

Other (OTH) AF: 0.000284 AC: 13 AN: 45801

GnomAD4 genome AF: 0.0000446 AC: 5 AN: 112073 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34251

African (AFR) AF: 0.00 AC: 0 AN: 30812

American (AMR) AF: 0.00 AC: 0 AN: 10585

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3589

South Asian (SAS) AF: 0.00 AC: 0 AN: 2692

European-Finnish (FIN) AF: 0.000825 AC: 5 AN: 6064

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53227

Other (OTH) AF: 0.00 AC: 0 AN: 1524

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZNF711: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.22
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0066
dbscSNV1_RF	Benign	0.086
SpliceAI score (max)		0.010		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: rs373653025; hg19: chrX-84502663;