X-92239655-A-G

Position:

• chrX-92239655-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032968.5(PCDH11X):​c.3115-23459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.74 (22066 hom., 23618 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH11X	NM_032968.5	c.3115-23459A>G		intron_variant		ENST00000682573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH11X	ENST00000682573.1	c.3115-23459A>G		intron_variant			NM_032968.5	P4

Frequencies

GnomAD3 genomes AF: 0.738 AC: 81421 AN: 110341 Hom.: 22075 Cov.: 23 AF XY: 0.723 AC XY: 23568 AN XY: 32601

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.719

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.738 AC: 81457 AN: 110387 Hom.: 22066 Cov.: 23 AF XY: 0.723 AC XY: 23618 AN XY: 32657

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.721

Alfa AF: 0.777 Hom.: 91813

Bravo AF: 0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.29
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs370928; hg19: chrX-91494654;