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GeneBe

X-91878301-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.458 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PCDH11XNM_032968.5 linkuse as main transcriptc.2061G>A p.Pro687= synonymous_variant 6/11 ENST00000682573.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PCDH11XENST00000682573.1 linkuse as main transcriptc.2061G>A p.Pro687= synonymous_variant 6/11 NM_032968.5 P4Q9BZA7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00743
AC:
818
AN:
110111
Hom.:
5
Cov.:
20
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.:
6
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.:
9
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00744
AC:
820
AN:
110167
Hom.:
5
Cov.:
20
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.:
24
Bravo
AF:
0.00798
EpiCase
AF:
0.000436
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs145794638; hg19: chrX-91133300; COSMIC: COSV53460892; API