X-85244123-AGGCGGCGGCGGCGGC-AGGCGGCGGCGGC

Variant names:

• chrX-85244123-AGGC-A
• rs758475553
• NM_001330574.2:c.-452_-450delGGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001330574.2(ZNF711):​c.-452_-450delGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000712 in 146,046 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., 3 hem., cov: 20)
  • Exomes 𝑓: 0.0021 (0 hom. 1 hem.)
• Consequence: ZNF711 NM_001330574.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933
• 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]

SATL1 (HGNC:27992): (spermidine/spermine N1-acetyl transferase like 1) Predicted to enable N-acetyltransferase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF711	NM_001330574.2	c.-452_-450delGGC		5_prime_UTR_variant	Exon 1 of 11	ENST00000674551.1	NP_001317503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF711	ENST00000674551.1	c.-452_-450delGGC		5_prime_UTR_variant	Exon 1 of 11		NM_001330574.2	ENSP00000502839.1
ZNF711	ENST00000276123.7	c.-447_-445delGGC		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000276123.3
ZNF711	ENST00000373165.7	c.-193_-191delGGC		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000362260.3
SATL1	ENST00000646235.1	c.-1434_-1432delGCC		upstream_gene_variant				ENSP00000495329.1

Frequencies

GnomAD3 genomes AF: 0.000221 AC: 24 AN: 108378 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.000613

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000294

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00429

Gnomad NFE AF: 0.0000768

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00213 AC: 80 AN: 37640 Hom.: 0 AF XY: 0.0000615 AC XY: 1 AN XY: 16270

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00150 AC: 1 AN: 668

American (AMR) AF: 0.00445 AC: 4 AN: 898

Ashkenazi Jewish (ASJ) AF: 0.00156 AC: 1 AN: 642

East Asian (EAS) AF: 0.00139 AC: 3 AN: 2160

South Asian (SAS) AF: 0.00226 AC: 4 AN: 1771

European-Finnish (FIN) AF: 0.00362 AC: 9 AN: 2488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 152

European-Non Finnish (NFE) AF: 0.00194 AC: 52 AN: 26757

Other (OTH) AF: 0.00285 AC: 6 AN: 2104

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000221 AC: 24 AN: 108406 Hom.: 0 Cov.: 20 AF XY: 0.0000952 AC XY: 3 AN XY: 31508

African (AFR) AF: 0.000612 AC: 18 AN: 29399

American (AMR) AF: 0.00 AC: 0 AN: 10406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2613

East Asian (EAS) AF: 0.000295 AC: 1 AN: 3385

South Asian (SAS) AF: 0.00 AC: 0 AN: 2534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5653

Middle Eastern (MID) AF: 0.00469 AC: 1 AN: 213

European-Non Finnish (NFE) AF: 0.0000768 AC: 4 AN: 52059

Other (OTH) AF: 0.00 AC: 0 AN: 1471

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.93
Mutation Taster		=300/0	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: rs758475553; hg19: chrX-84499129;