chrX-47926203-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

ZNF81 Gene-Disease associations (from GenCC):

• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, X-linked 45

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• X-linked intellectual disability

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376950.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF81	ENST00000376950.4	TSL:5	c.277+30263G>C		intron	N/A	ENSP00000366149.4	B1AJV2

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 8105 AN: 111309 Hom.: 561 Cov.: 23

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

African (AFR) AF: 0.216 AC: 6623 AN: 30625

American (AMR) AF: 0.0337 AC: 354 AN: 10514

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 98 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.00260 AC: 7 AN: 2690

European-Finnish (FIN) AF: 0.0295 AC: 174 AN: 5903

Middle Eastern (MID) AF: 0.0469 AC: 10 AN: 213

European-Non Finnish (NFE) AF: 0.0145 AC: 771 AN: 52990

Other (OTH) AF: 0.0570 AC: 87 AN: 1527

Alfa AF: 0.0499 Hom.: 243

Bravo AF: 0.0824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.4
DANN	Benign	0.91
PhyloP100		-0.37

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs619200;

hg19: chrX-47785602;