X-91876892-AA-CG

Variant names:

• chrX-91876892-AA-CG
• NM_032968.5:c.652_653delAAinsCG
• PCDH11X p.Lys218Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_032968.5(PCDH11X):​c.652_653delAAinsCG​(p.Lys218Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. K218I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 20)
• Consequence: PCDH11X NM_032968.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.04
• Publications: 0 publications found

Genes affected

PCDH11X (HGNC:8656): (protocadherin 11 X-linked) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog, despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell-cell recognition essential for the segmental development and function of the central nervous system. Disruption of this gene may be associated with developmental dyslexia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032968.5. 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
	PCDH11X	NM_032968.5	MANE Select	c.652_653delAAinsCG	p.Lys218Arg	missense	N/A	NP_116750.1	Q9BZA7-1
	PCDH11X	NM_001168360.1		c.652_653delAAinsCG	p.Lys218Arg	missense	N/A	NP_001161832.1	Q9BZA7-8
	PCDH11X	NM_032969.4		c.652_653delAAinsCG	p.Lys218Arg	missense	N/A	NP_116751.1	Q9BZA7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH11X	ENST00000682573.1	MANE Select	c.652_653delAAinsCG	p.Lys218Arg	missense	N/A	ENSP00000507225.1	Q9BZA7-1
	PCDH11X	ENST00000373094.5	TSL:1	c.652_653delAAinsCG	p.Lys218Arg	missense	N/A	ENSP00000362186.1	Q9BZA7-1
	PCDH11X	ENST00000406881.3	TSL:1	c.652_653delAAinsCG	p.Lys218Arg	missense	N/A	ENSP00000384758.1	Q9BZA7-8

Frequencies

GnomAD3 genomes Cov.: 20

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

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

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-91131891;