rs453810

Positions:

• chrX-92241064-T-G

Variant summary

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

The NM_032968.5(PCDH11X):​c.3115-22050T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 109,884 control chromosomes in the GnomAD database, including 15,525 homozygotes. There are 18,179 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 0.58 (15525 hom., 18179 hem., cov: 22)
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.3115-22050T>G		intron_variant		ENST00000682573.1	NP_116750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1	c.3115-22050T>G		intron_variant			NM_032968.5	ENSP00000507225.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 64064 AN: 109837 Hom.: 15535 Cov.: 22 AF XY: 0.565 AC XY: 18157 AN XY: 32137

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.583 AC: 64067 AN: 109884 Hom.: 15525 Cov.: 22 AF XY: 0.565 AC XY: 18179 AN XY: 32194

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.588

Alfa AF: 0.736 Hom.: 82750

Bravo AF: 0.544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.0
DANN	Benign	0.72

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: rs453810; hg19: chrX-91496063;