Variant X-91878301-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032968.5(PCDH11X):c.2061G>A(p.Pro687=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,208,256 control chromosomes in the GnomAD database, including 14 homozygotes. There are 576 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 5 hom., 220 hem., cov: 20)

Exomes 𝑓: 0.0011 ( 9 hom. 356 hem. )

Consequence

PCDH11X
NM_032968.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.458

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 -21 ACMG points.

BP4

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

BP6

Variant X-91878301-G-A is Benign according to our data. Variant chrX-91878301-G-A is described in ClinVar as [Benign]. Clinvar id is 787161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.458 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00744 (820/110167) while in subpopulation AFR AF= 0.0231 (698/30272). AF 95% confidence interval is 0.0216. There are 5 homozygotes in gnomad4. There are 220 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH11X	NM_032968.5 linkuse as main transcript	c.2061G>A	p.Pro687=	synonymous_variant	6/11	ENST00000682573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH11X	ENST00000682573.1 linkuse as main transcript	c.2061G>A	p.Pro687=	synonymous_variant	6/11		NM_032968.5	P4	Q9BZA7-1

Frequencies

GnomAD3 genomes

AF:

0.00743

AC:

818

AN:

110111

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

218

AN XY:

32343

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00858

Gnomad NFE

AF:

0.000549

Gnomad OTH

AF:

0.00609

GnomAD3 exomes

AF:

0.00232

AC:

426

AN:

183279

Hom.:

AF XY:

0.00177

AC XY:

120

AN XY:

67847

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00628

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000208

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00112

AC:

1231

AN:

1098089

Hom.:

Cov.:

AF XY:

0.000979

AC XY:

356

AN XY:

363565

show subpopulations

Gnomad4 AFR exome

AF:

0.0256

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00665

Gnomad4 EAS exome

AF:

0.000132

Gnomad4 SAS exome

AF:

0.000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000260

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.00744

AC:

820

AN:

110167

Hom.:

Cov.:

AF XY:

0.00679

AC XY:

220

AN XY:

32409

show subpopulations

Gnomad4 AFR

AF:

0.0231

Gnomad4 AMR

AF:

0.00615

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000549

Gnomad4 OTH

AF:

0.00601

Alfa

AF:

0.00458

Hom.:

Bravo

AF:

0.00798

EpiCase

AF:

0.000436

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.91

DANN

Benign

0.44

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over