X-92147221-T-C

Position:

• chrX-92147221-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032968.5(PCDH11X):​c.3034-54154T>C 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 0.51 (12074 hom., 13295 hem., cov: 20)
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.3034-54154T>C		intron_variant		ENST00000682573.1	NP_116750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1	c.3034-54154T>C		intron_variant			NM_032968.5	ENSP00000507225.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 54703 AN: 106370 Hom.: 12081 Cov.: 20 AF XY: 0.453 AC XY: 13265 AN XY: 29286

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.448

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.514 AC: 54715 AN: 106416 Hom.: 12074 Cov.: 20 AF XY: 0.453 AC XY: 13295 AN XY: 29344

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.474

Alfa AF: 0.496 Hom.: 34165

Bravo AF: 0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.64

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: rs2573905; hg19: chrX-91402220;