rs10522057

Variant names:

• chrX-92248202-G-A
• rs10522057
• NM_032968.5:c.3115-14912G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032968.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH11X	NM_032968.5	MANE Select	c.3115-14912G>A		intron	N/A	NP_116750.1
	PCDH11X	NM_001168360.1		c.3115-14912G>A		intron	N/A	NP_001161832.1
	PCDH11X	NM_032969.4		c.3114+46747G>A		intron	N/A	NP_116751.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH11X	ENST00000682573.1	MANE Select	c.3115-14912G>A		intron	N/A	ENSP00000507225.1
	PCDH11X	ENST00000373094.5	TSL:1	c.3115-14912G>A		intron	N/A	ENSP00000362186.1
	PCDH11X	ENST00000406881.3	TSL:1	c.3115-14912G>A		intron	N/A	ENSP00000384758.1

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 5773 AN: 110806 Hom.: 258 Cov.: 22

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

African (AFR) AF: 0.0639 AC: 1949 AN: 30493

American (AMR) AF: 0.187 AC: 1930 AN: 10320

Ashkenazi Jewish (ASJ) AF: 0.00152 AC: 4 AN: 2640

East Asian (EAS) AF: 0.215 AC: 742 AN: 3458

South Asian (SAS) AF: 0.136 AC: 353 AN: 2595

European-Finnish (FIN) AF: 0.0273 AC: 161 AN: 5888

Middle Eastern (MID) AF: 0.0237 AC: 5 AN: 211

European-Non Finnish (NFE) AF: 0.0101 AC: 537 AN: 53057

Other (OTH) AF: 0.0603 AC: 91 AN: 1508

Alfa AF: 0.0380 Hom.: 250

Bravo AF: 0.0681

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.52
PhyloP100		-0.29
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: rs10522057; hg19: chrX-91503201;