rs370928

Variant names:

• chrX-92239655-A-G
• rs370928
• NM_032968.5:c.3115-23459A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032968.5(PCDH11X):​c.3115-23459A>G 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 0.74 (22066 hom., 23618 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: PCDH11X NM_032968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.3115-23459A>G		intron_variant	Intron 7 of 10	ENST00000682573.1	NP_116750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1	c.3115-23459A>G		intron_variant	Intron 7 of 10		NM_032968.5	ENSP00000507225.1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 81421 AN: 110341 Hom.: 22075 Cov.: 23

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.719

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.738 AC: 81457 AN: 110387 Hom.: 22066 Cov.: 23 AF XY: 0.723 AC XY: 23618 AN XY: 32657

African (AFR) AF: 0.747 AC: 22722 AN: 30430

American (AMR) AF: 0.496 AC: 5108 AN: 10298

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 1979 AN: 2629

East Asian (EAS) AF: 0.394 AC: 1366 AN: 3469

South Asian (SAS) AF: 0.718 AC: 1881 AN: 2620

European-Finnish (FIN) AF: 0.717 AC: 4182 AN: 5834

Middle Eastern (MID) AF: 0.887 AC: 189 AN: 213

European-Non Finnish (NFE) AF: 0.805 AC: 42422 AN: 52721

Other (OTH) AF: 0.721 AC: 1082 AN: 1501

Alfa AF: 0.771 Hom.: 113963

Bravo AF: 0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.29
DANN	Benign	0.29
PhyloP100		-0.24
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: rs370928; hg19: chrX-91494654;