rs368890164

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018933.4(PCDHB13):c.143A>G(p.Asn48Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000102 in 1,571,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

PCDHB13
NM_018933.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Publications

0 publications found

Variant links:

Genes affected

PCDHB13 (HGNC:8684): (protocadherin beta 13) This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The beta cluster contains 16 genes and 3 pseudogenes, each encoding 6 extracellular cadherin domains and a cytoplasmic tail that deviates from others in the cadherin superfamily. The extracellular domains interact in a homophilic manner to specify differential cell-cell connections. Unlike the alpha and gamma clusters, the transcripts from these genes are made up of only one large exon, not sharing common 3' exons as expected. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins. Their specific functions are unknown but they most likely play a critical role in the establishment and function of specific cell-cell neural connections. [provided by RefSeq, Jul 2008]

PCDHB13 links:

PCDHB@ (HGNC:8679):

PCDHB@ links:

ENSG00000280029 (HGNC:):

ENSG00000280029 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23511809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDHB13	NM_018933.4 link	c.143A>G	p.Asn48Ser	missense_variant	Exon 1 of 1	ENST00000341948.6	NP_061756.1	Q9Y5F0
PCDHB@		n.141214266A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCDHB13	ENST00000341948.6 link	c.143A>G	p.Asn48Ser	missense_variant	Exon 1 of 1	6	NM_018933.4	ENSP00000345491.4	Q9Y5F0
ENSG00000280029	ENST00000624192.1 link	n.72+27407T>C		intron_variant	Intron 1 of 1	5
ENSG00000272154	ENST00000718175.1 link	n.71+21753T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0000203

AC:

AN:

147720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000178

AC:

AN:

224668

AF XY:

0.0000163

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:

0.00

Gnomad NFE exome

AF:

0.0000405

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000913

AC:

AN:

1423562

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

709480

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32708

American (AMR)

AF:

0.00

AC:

AN:

44266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25878

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39488

South Asian (SAS)

AF:

0.00

AC:

AN:

84880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.00000927

AC:

AN:

1078474

Other (OTH)

AF:

0.0000169

AC:

AN:

59002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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:

0.0000203

AC:

AN:

147720

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71800

show subpopulations

African (AFR)

AF:

0.0000252

AC:

AN:

39666

American (AMR)

AF:

0.00

AC:

AN:

14756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.000196

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67090

Other (OTH)

AF:

0.00

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000247

AC:

ExAC

AF:

0.0000251

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 01, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.143A>G (p.N48S) alteration is located in exon 1 (coding exon 1) of the PCDHB13 gene. This alteration results from a A to G substitution at nucleotide position 143, causing the asparagine (N) at amino acid position 48 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.028

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.26

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

M_CAP

Benign

0.013

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.2

PhyloP100

5.1

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.17

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.032

Polyphen

0.028

Vest4

0.26

MVP

0.63

ClinPred

0.29

GERP RS

3.5

PromoterAI

0.0046

Neutral

(source)

Varity_R

0.18

gMVP

0.34

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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