X-47926203-G-C

Position:

• chrX-47926203-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000376950.4(ZNF81):​c.277+30263G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 111,358 control chromosomes in the GnomAD database, including 561 homozygotes. There are 2,256 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 0.073 (561 hom., 2256 hem., cov: 23)
• Consequence: ZNF81 ENST00000376950.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

Genes affected

ZNF81 (HGNC:13156): (zinc finger protein 81) This gene encodes a protein that likely functions as a transcription factor. The protein contains an N-terminal KRAB domain and several C2H2-type zinc finger motifs. Mutations in this gene cause an X-linked form of intellectual disability (MRX45). Microduplication of a region of chromosome X including this gene has also been associated with other forms of intellectual disability. [provided by RefSeq, Jul 2017]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.47926203G>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF81	ENST00000376950.4	c.277+30263G>C		intron_variant		5		ENSP00000366149.4

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 8105 AN: 111309 Hom.: 561 Cov.: 23 AF XY: 0.0666 AC XY: 2239 AN XY: 33617

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00259

Gnomad FIN AF: 0.0295

Gnomad MID AF: 0.0596

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0577

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

GnomAD4 genome AF: 0.0730 AC: 8124 AN: 111358 Hom.: 561 Cov.: 23 AF XY: 0.0670 AC XY: 2256 AN XY: 33676

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0337

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00260

Gnomad4 FIN AF: 0.0295

Gnomad4 NFE AF: 0.0145

Gnomad4 OTH AF: 0.0570

Alfa AF: 0.0499 Hom.: 243

Bravo AF: 0.0824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.4
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs619200; hg19: chrX-47785602;