X-47926203-G-C

Variant names:

• chrX-47926203-G-C
• rs619200
• ENST00000376950.4:c.277+30263G>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]

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF81	ENST00000376950.4	c.277+30263G>C		intron_variant	Intron 4 of 4	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;