NM_032968.5:c.2279A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_032968.5(PCDH11X):c.2279A>T(p.Asp760Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000207 in 1,208,168 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000020 ( 0 hom. 7 hem. )

Consequence

PCDH11X
NM_032968.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.04

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24232692).

BP6

Variant X-91878519-A-T is Benign according to our data. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-91878519-A-T is described in CliVar as Likely_benign. Clinvar id is 427850.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH11X	NM_032968.5 link	c.2279A>T	p.Asp760Val	missense_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.2279A>T	p.Asp760Val	missense_variant	Exon 6 of 11		NM_032968.5	ENSP00000507225.1		Q9BZA7-1

Frequencies

GnomAD3 genomes

AF:

0.0000273

AC:

AN:

110079

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000172

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000379

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

183173

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1098089

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363563

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26397

American (AMR)

AF:

0.00

AC:

AN:

35201

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54142

European-Finnish (FIN)

AF:

0.000444

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000475

AC:

AN:

842009

Other (OTH)

AF:

0.00

AC:

AN:

46086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000273

AC:

AN:

110079

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

32281

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30175

American (AMR)

AF:

0.00

AC:

AN:

10220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2625

East Asian (EAS)

AF:

0.00

AC:

AN:

3490

South Asian (SAS)

AF:

0.00

AC:

AN:

2531

European-Finnish (FIN)

AF:

0.000172

AC:

AN:

5826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000379

AC:

AN:

52808

Other (OTH)

AF:

0.00

AC:

AN:

1486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Alzheimer disease

Benign:1

Myllykangas group, University of Helsinki

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

.;T;.;.;.;.

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D;D;D;D;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.24

T;T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.17

N;N;N;N;N;N

PhyloP100

7.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

N;N;N;N;N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0080

D;D;D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D;D

Polyphen

0.91

P;P;P;P;P;P

Vest4

0.20

MutPred

0.47

Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);

MVP

0.59

MPC

2.6

ClinPred

0.56

GERP RS

4.8

Varity_R

0.43

gMVP

0.59

Mutation Taster

=70/30

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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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