NM_032968.5:c.3034-24989C>T

Variant names:

• chrX-92176386-C-T
• rs5941047
• NM_032968.5:c.3034-24989C>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.3034-24989C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 110,349 control chromosomes in the GnomAD database, including 10,601 homozygotes. There are 15,884 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 0.50 (10601 hom., 15884 hem., cov: 22)
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.3034-24989C>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.3034-24989C>T		intron_variant	Intron 6 of 10		NM_032968.5	ENSP00000507225.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 55619 AN: 110296 Hom.: 10608 Cov.: 22

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.504 AC: 55631 AN: 110349 Hom.: 10601 Cov.: 22 AF XY: 0.486 AC XY: 15884 AN XY: 32663

African (AFR) AF: 0.385 AC: 11716 AN: 30411

American (AMR) AF: 0.363 AC: 3758 AN: 10340

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1256 AN: 2627

East Asian (EAS) AF: 0.546 AC: 1885 AN: 3452

South Asian (SAS) AF: 0.418 AC: 1092 AN: 2615

European-Finnish (FIN) AF: 0.510 AC: 2944 AN: 5774

Middle Eastern (MID) AF: 0.587 AC: 125 AN: 213

European-Non Finnish (NFE) AF: 0.603 AC: 31785 AN: 52746

Other (OTH) AF: 0.484 AC: 727 AN: 1502

Alfa AF: 0.522 Hom.: 18217

Bravo AF: 0.489

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.0
DANN	Benign	0.71
PhyloP100		-0.058
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: rs5941047; hg19: chrX-91431385;