X-47915115-AAT-TCC

Variant names:

• chrX-47915115-AAT-TCC
• NM_007137.5:c.469_471delAATinsTCC
• ZNF81 p.Asn157Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_007137.5(ZNF81):​c.469_471delAATinsTCC​(p.Asn157Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZNF81 NM_007137.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007137.5. 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
	ZNF81	NM_007137.5	MANE Select	c.469_471delAATinsTCC	p.Asn157Ser	missense	N/A	NP_009068.2	P51508
	ZNF81	NM_001378152.1		c.469_471delAATinsTCC	p.Asn157Ser	missense	N/A	NP_001365081.1	P51508
	ZNF81	NM_001378153.1		c.469_471delAATinsTCC	p.Asn157Ser	missense	N/A	NP_001365082.1	P51508

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF81	ENST00000338637.13	TSL:3 MANE Select	c.469_471delAATinsTCC	p.Asn157Ser	missense	N/A	ENSP00000341151.7	P51508
	ZNF81	ENST00000376954.6	TSL:5	c.469_471delAATinsTCC	p.Asn157Ser	missense	N/A	ENSP00000366153.1	P51508
	ZNF81	ENST00000853619.1		c.469_471delAATinsTCC	p.Asn157Ser	missense	N/A	ENSP00000523678.1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

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

hg19: chrX-47774514;