dbSNP rs367906861: PCDH11X:p.Ala337Ala (chrX-91877251-A-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_032968.5(PCDH11X):c.1011A>G(p.Ala337Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., 30 hem., cov: 14)

Exomes 𝑓: 0.00030 ( 1 hom. 57 hem. )

Consequence

PCDH11X
NM_032968.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.147

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant X-91877251-A-G is Benign according to our data. Variant chrX-91877251-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 724999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.147 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH11X	NM_032968.5 link	c.1011A>G	p.Ala337Ala	synonymous_variant	Exon 6 of 11	ENST00000682573.1	NP_116750.1	Q9BZA7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1 link	c.1011A>G	p.Ala337Ala	synonymous_variant	Exon 6 of 11		NM_032968.5	ENSP00000507225.1		Q9BZA7-1

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

201

AN:

91806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00782

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000383

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000431

Gnomad OTH

AF:

0.00174

GnomAD2 exomes

AF:

0.000783

AC:

AN:

103477

AF XY:

0.000397

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000243

Gnomad OTH exome

AF:

0.000665

GnomAD4 exome

AF:

0.000297

AC:

291

AN:

981124

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

286872

show subpopulations

African (AFR)

AF:

0.00979

AC:

233

AN:

23805

American (AMR)

AF:

0.000473

AC:

AN:

31682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18137

East Asian (EAS)

AF:

0.00

AC:

AN:

28317

South Asian (SAS)

AF:

0.00

AC:

AN:

49006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37019

Middle Eastern (MID)

AF:

0.00107

AC:

AN:

3735

European-Non Finnish (NFE)

AF:

0.00000803

AC:

AN:

747252

Other (OTH)

AF:

0.000783

AC:

AN:

42171

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00219

AC:

201

AN:

91843

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

AN XY:

17231

show subpopulations

African (AFR)

AF:

0.00780

AC:

194

AN:

24872

American (AMR)

AF:

0.000383

AC:

AN:

7835

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2331

East Asian (EAS)

AF:

0.00

AC:

AN:

2931

South Asian (SAS)

AF:

0.00

AC:

AN:

1627

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3915

Middle Eastern (MID)

AF:

0.00

AC:

AN:

202

European-Non Finnish (NFE)

AF:

0.0000431

AC:

AN:

46363

Other (OTH)

AF:

0.00172

AC:

AN:

1166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00158

Hom.:

Bravo

AF:

0.00287

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.0

(source)

DANN

Benign

0.27

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism

(source)

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

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rs367906861

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over