rs726546

Variant names:

• chrX-135338261-T-A
• rs726546
• NM_007131.5:c.-391+3507A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007131.5(ZNF75D):​c.-391+3507A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 110,006 control chromosomes in the GnomAD database, including 2,931 homozygotes. There are 8,190 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (2931 hom., 8190 hem., cov: 22)
• Consequence: ZNF75D NM_007131.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468
• Publications: 1 publications found

Genes affected

ZNF75D (HGNC:13145): (zinc finger protein 75D) This gene encodes a protein that likely functions as a transcription factor. The protein, which belongs to the ZNF75 family, includes an N-terminal SCAN domain, a KRAB box, and five C2H2-type zinc finger motifs. Another functional gene belonging to this family is located on chromosome 16, while pseudogenes have been identified on chromosomes 11 and 12. Alternative splicing results in multiple transcripts variants. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007131.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF75D	NM_007131.5	MANE Select	c.-391+3507A>T		intron	N/A	NP_009062.2
	ZNF75D	NR_110381.2		n.849+5000A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF75D	ENST00000370766.8	TSL:1 MANE Select	c.-391+3507A>T		intron	N/A	ENSP00000359802.3
	ZNF75D	ENST00000494295.2	TSL:2	n.827+5000A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.260 AC: 28629 AN: 109947 Hom.: 2936 Cov.: 22

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.260 AC: 28618 AN: 110006 Hom.: 2931 Cov.: 22 AF XY: 0.253 AC XY: 8190 AN XY: 32316

African (AFR) AF: 0.156 AC: 4741 AN: 30325

American (AMR) AF: 0.210 AC: 2183 AN: 10386

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 807 AN: 2622

East Asian (EAS) AF: 0.364 AC: 1251 AN: 3433

South Asian (SAS) AF: 0.437 AC: 1113 AN: 2549

European-Finnish (FIN) AF: 0.317 AC: 1815 AN: 5725

Middle Eastern (MID) AF: 0.408 AC: 87 AN: 213

European-Non Finnish (NFE) AF: 0.304 AC: 16005 AN: 52597

Other (OTH) AF: 0.302 AC: 451 AN: 1492

Alfa AF: 0.274 Hom.: 1730

Bravo AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.80
PhyloP100		-0.47
Mutation Taster		=100/0	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: rs726546; hg19: chrX-134472186;