X-92176386-C-T

Variant names:

• chrX-92176386-C-T
• rs5941047
• NM_032968.5:c.3034-24989C>T

Variant summary

Our verdict is Benign. Variant got -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

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=-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 AF XY: 0.486 AC XY: 15852 AN XY: 32600

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

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.484

Alfa AF: 0.526 Hom.: 11838

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

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: rs5941047; hg19: chrX-91431385;