chrX-92147221-T-C

Variant names:

• chrX-92147221-T-C
• rs2573905
• NM_032968.5:c.3034-54154T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032968.5(PCDH11X):​c.3034-54154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.51 (12074 hom., 13295 hem., cov: 20)
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 15 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 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.3034-54154T>C		intron	N/A	NP_116750.1	Q9BZA7-1
	PCDH11X	NM_001168360.1		c.3034-54154T>C		intron	N/A	NP_001161832.1	Q9BZA7-8
	PCDH11X	NM_032969.4		c.3034-54154T>C		intron	N/A	NP_116751.1	Q9BZA7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH11X	ENST00000682573.1	MANE Select	c.3034-54154T>C		intron	N/A	ENSP00000507225.1	Q9BZA7-1
	PCDH11X	ENST00000373094.5	TSL:1	c.3034-54154T>C		intron	N/A	ENSP00000362186.1	Q9BZA7-1
	PCDH11X	ENST00000406881.3	TSL:1	c.3034-54154T>C		intron	N/A	ENSP00000384758.1	Q9BZA7-8

Frequencies

GnomAD3 genomes AF: 0.514 AC: 54703 AN: 106370 Hom.: 12081 Cov.: 20

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.448

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.514 AC: 54715 AN: 106416 Hom.: 12074 Cov.: 20 AF XY: 0.453 AC XY: 13295 AN XY: 29344

African (AFR) AF: 0.704 AC: 19752 AN: 28046

American (AMR) AF: 0.328 AC: 3290 AN: 10038

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 964 AN: 2615

East Asian (EAS) AF: 0.111 AC: 384 AN: 3475

South Asian (SAS) AF: 0.263 AC: 649 AN: 2464

European-Finnish (FIN) AF: 0.401 AC: 2199 AN: 5482

Middle Eastern (MID) AF: 0.455 AC: 96 AN: 211

European-Non Finnish (NFE) AF: 0.507 AC: 26379 AN: 51993

Other (OTH) AF: 0.474 AC: 683 AN: 1440

Alfa AF: 0.512 Hom.: 44663

Bravo AF: 0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		-0.14
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: rs2573905; hg19: chrX-91402220;