X-85244148-A-G

Variant names:

• chrX-85244148-A-G
• rs375972814
• NM_001330574.2:c.-449A>G

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.-449A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (76 hom., 545 hem., cov: 20)
  • Exomes 𝑓: 0.028 (29 hom. 451 hem.)
• Consequence: ZNF711 NM_001330574.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.661
• 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]

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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant X-85244148-A-G is Benign according to our data. Variant chrX-85244148-A-G is described in ClinVar as [Benign]. Clinvar id is 368741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF711	NM_001330574.2	c.-449A>G		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.-449A>G		5_prime_UTR_variant	Exon 1 of 11		NM_001330574.2	ENSP00000502839.1
ZNF711	ENST00000276123.7	c.-444A>G		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000276123.3
ZNF711	ENST00000373165.7	c.-190A>G		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000362260.3
SATL1	ENST00000646235.1	c.-1456T>C		upstream_gene_variant				ENSP00000495329.1

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 3006 AN: 96981 Hom.: 76 Cov.: 20

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.00501

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0111

Gnomad EAS AF: 0.000613

Gnomad SAS AF: 0.00386

Gnomad FIN AF: 0.00911

Gnomad MID AF: 0.0193

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0256

GnomAD4 exome AF: 0.0280 AC: 990 AN: 35396 Hom.: 29 Cov.: 0 AF XY: 0.0283 AC XY: 451 AN XY: 15910

African (AFR) AF: 0.110 AC: 65 AN: 589

American (AMR) AF: 0.0393 AC: 24 AN: 610

Ashkenazi Jewish (ASJ) AF: 0.0413 AC: 25 AN: 606

East Asian (EAS) AF: 0.00140 AC: 3 AN: 2144

South Asian (SAS) AF: 0.00623 AC: 9 AN: 1444

European-Finnish (FIN) AF: 0.0464 AC: 105 AN: 2263

Middle Eastern (MID) AF: 0.0407 AC: 7 AN: 172

European-Non Finnish (NFE) AF: 0.0276 AC: 706 AN: 25590

Other (OTH) AF: 0.0233 AC: 46 AN: 1978

GnomAD4 genome AF: 0.0310 AC: 3007 AN: 97030 Hom.: 76 Cov.: 20 AF XY: 0.0187 AC XY: 545 AN XY: 29206

African (AFR) AF: 0.0832 AC: 2106 AN: 25303

American (AMR) AF: 0.0155 AC: 125 AN: 8064

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 28 AN: 2533

East Asian (EAS) AF: 0.000616 AC: 2 AN: 3249

South Asian (SAS) AF: 0.00387 AC: 9 AN: 2323

European-Finnish (FIN) AF: 0.00911 AC: 48 AN: 5270

Middle Eastern (MID) AF: 0.0215 AC: 4 AN: 186

European-Non Finnish (NFE) AF: 0.0135 AC: 649 AN: 48194

Other (OTH) AF: 0.0252 AC: 33 AN: 1309

Alfa AF: 0.0325 Hom.: 90

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Intellectual disability, X-linked 97 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.2
DANN	Benign	0.66
PhyloP100		-0.66
PromoterAI		0.084	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs375972814; hg19: chrX-84499154;