Variant rs4252206 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032968.5(PCDH11X):c.3114+4T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,138,907 control chromosomes in the GnomAD database, including 1,406 homozygotes. There are 14,481 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.066 ( 322 hom., 2122 hem., cov: 23)

Exomes 𝑓: 0.037 ( 1084 hom. 12359 hem. )

Consequence

PCDH11X
NM_032968.5 splice_region, intron

Scores

Splicing: ADA: 0.0001352

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.241

Variant links:

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]

PCDH11X links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH11X	NM_032968.5 linkuse as main transcript	c.3114+4T>G		splice_region_variant, intron_variant		ENST00000682573.1	NP_116750.1	Q9BZA7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1 linkuse as main transcript	c.3114+4T>G		splice_region_variant, intron_variant			NM_032968.5	ENSP00000507225.1		Q9BZA7-1

Frequencies

GnomAD3 genomes

AF:

0.0662

AC:

7384

AN:

111541

Hom.:

325

Cov.:

AF XY:

0.0627

AC XY:

2116

AN XY:

33755

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.0593

Gnomad NFE

AF:

0.0216

Gnomad OTH

AF:

0.0662

GnomAD3 exomes

AF:

0.0575

AC:

9301

AN:

161840

Hom.:

440

AF XY:

0.0511

AC XY:

2655

AN XY:

51934

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.0519

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.0229

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0367

AC:

37732

AN:

1027316

Hom.:

1084

Cov.:

AF XY:

0.0407

AC XY:

12359

AN XY:

303844

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.0356

Gnomad4 ASJ exome

AF:

0.0557

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0226

Gnomad4 NFE exome

AF:

0.0214

Gnomad4 OTH exome

AF:

0.0531

GnomAD4 genome

AF:

0.0662

AC:

7383

AN:

111591

Hom.:

322

Cov.:

AF XY:

0.0628

AC XY:

2122

AN XY:

33815

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.0370

Gnomad4 ASJ

AF:

0.0519

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.0219

Gnomad4 NFE

AF:

0.0216

Gnomad4 OTH

AF:

0.0672

Alfa

AF:

0.0389

Hom.:

805

Bravo

AF:

0.0753

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.6

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over