rs4568761

Positions:

• chrX-92184068-C-T

Variant summary

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

The NM_032968.5(PCDH11X):​c.3034-17307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 110,252 control chromosomes in the GnomAD database, including 8,338 homozygotes. There are 13,037 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 0.42 (8338 hom., 13037 hem., cov: 22)
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.3034-17307C>T		intron_variant		ENST00000682573.1	NP_116750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1	c.3034-17307C>T		intron_variant			NM_032968.5	ENSP00000507225	P4

Frequencies

GnomAD3 genomes AF: 0.417 AC: 46000 AN: 110199 Hom.: 8341 Cov.: 22 AF XY: 0.401 AC XY: 13025 AN XY: 32499

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.417 AC: 45995 AN: 110252 Hom.: 8338 Cov.: 22 AF XY: 0.400 AC XY: 13037 AN XY: 32562

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.423

Alfa AF: 0.520 Hom.: 13712

Bravo AF: 0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.64
DANN	Benign	0.48

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: rs4568761; hg19: chrX-91439067;