chrX-47926203-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000376950.4(ZNF81):​c.277+30263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 111,337 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.000018 (0 hom., 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).

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>A		intron	N/A	ENSP00000366149.4	B1AJV2

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111337 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111337 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33635

African (AFR) AF: 0.00 AC: 0 AN: 30576

American (AMR) AF: 0.00 AC: 0 AN: 10504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3588

South Asian (SAS) AF: 0.00 AC: 0 AN: 2701

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5903

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53003

Other (OTH) AF: 0.00 AC: 0 AN: 1508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.5
DANN	Benign	0.86
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;