chrX-92248202-G-A

Position:

• chrX-92248202-G-A

Variant summary

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

The NM_032968.5(PCDH11X):​c.3115-14912G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 110,856 control chromosomes in the GnomAD database, including 257 homozygotes. There are 1,821 hemizygotes 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 0.052 (257 hom., 1821 hem., cov: 22)
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH11X	NM_032968.5	c.3115-14912G>A		intron_variant		ENST00000682573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH11X	ENST00000682573.1	c.3115-14912G>A		intron_variant			NM_032968.5	P4

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 5773 AN: 110806 Hom.: 258 Cov.: 22 AF XY: 0.0551 AC XY: 1820 AN XY: 33032

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.00152

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0611

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

GnomAD4 genome AF: 0.0521 AC: 5773 AN: 110856 Hom.: 257 Cov.: 22 AF XY: 0.0550 AC XY: 1821 AN XY: 33092

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.00152

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.0603

Alfa AF: 0.0380 Hom.: 250

Bravo AF: 0.0681

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.52

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: rs10522057; hg19: chrX-91503201;