rs4568761

Variant names:

• chrX-92184068-C-T
• rs4568761
• NM_032968.5:c.3034-17307C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.3034-17307C>T		intron_variant	Intron 6 of 10	ENST00000682573.1	NP_116750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1	c.3034-17307C>T		intron_variant	Intron 6 of 10		NM_032968.5	ENSP00000507225.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 46000 AN: 110199 Hom.: 8341 Cov.: 22

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

African (AFR) AF: 0.192 AC: 5825 AN: 30353

American (AMR) AF: 0.317 AC: 3275 AN: 10346

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1136 AN: 2626

East Asian (EAS) AF: 0.116 AC: 409 AN: 3511

South Asian (SAS) AF: 0.278 AC: 735 AN: 2641

European-Finnish (FIN) AF: 0.483 AC: 2727 AN: 5645

Middle Eastern (MID) AF: 0.533 AC: 113 AN: 212

European-Non Finnish (NFE) AF: 0.584 AC: 30797 AN: 52751

Other (OTH) AF: 0.423 AC: 634 AN: 1500

Alfa AF: 0.496 Hom.: 19165

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
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4568761; hg19: chrX-91439067;