rs5984894

Positions:

• chrX-92138738-A-G

Variant summary

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

The NM_032968.5(PCDH11X):​c.3034-62637A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 109,929 control chromosomes in the GnomAD database, including 12,273 homozygotes. There are 16,070 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 0.53 (12273 hom., 16070 hem., cov: 23)
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.3034-62637A>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.3034-62637A>G		intron_variant			NM_032968.5	ENSP00000507225.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 57985 AN: 109881 Hom.: 12280 Cov.: 23 AF XY: 0.498 AC XY: 16037 AN XY: 32191

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.451

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.528 AC: 58001 AN: 109929 Hom.: 12273 Cov.: 23 AF XY: 0.498 AC XY: 16070 AN XY: 32249

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.488

Alfa AF: 0.511 Hom.: 15922

Bravo AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.048
DANN	Benign	0.46

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: rs5984894; hg19: chrX-91393737;