Variant 5-141214266-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/20 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

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:):

PCDHB@ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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/exons	MANE	Protein	UniProt
PCDHB13	NM_018933.4 linkuse as main transcript	c.143A>G	p.Asn48Ser	missense_variant	1/1	ENST00000341948.6	NP_061756.1	Q9Y5F0
PCDHB@	use as main transcript	n.141214266A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDHB13	ENST00000341948.6 linkuse as main transcript	c.143A>G	p.Asn48Ser	missense_variant	1/1	6	NM_018933.4	ENSP00000345491.4		Q9Y5F0
ENSG00000280029	ENST00000624192.1 linkuse as main transcript	n.72+27407T>C		intron_variant		5

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

GnomAD3 exomes

AF:

0.0000178

AC:

AN:

224668

Hom.:

AF XY:

0.0000163

AC XY:

AN XY:

122648

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000927

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000203

AC:

AN:

147720

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71800

show subpopulations

Gnomad4 AFR

AF:

0.0000252

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

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

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

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

Varity_R

0.18

gMVP

0.34

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

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