GeneBe

rs3733698

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018938.4(PCDHB4):​c.763C>A​(p.Pro255Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P255S) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PCDHB4
NM_018938.4 missense

Scores

1
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.705

Publications

21 publications found
Variant links:
Genes affected
PCDHB4 (HGNC:8689): (protocadherin beta 4) 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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018938.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PCDHB4
NM_018938.4
MANE Select
c.763C>Ap.Pro255Thr
missense
Exon 1 of 1NP_061761.1Q9Y5E5

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PCDHB4
ENST00000194152.4
TSL:6 MANE Select
c.763C>Ap.Pro255Thr
missense
Exon 1 of 1ENSP00000194152.1Q9Y5E5
PCDHB4
ENST00000623478.1
TSL:1
n.214-394C>A
intron
N/A
ENSG00000272154
ENST00000624802.1
TSL:3
n.365-22006G>T
intron
N/A

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
8479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.047
T
Eigen
Benign
-0.0051
Eigen_PC
Benign
-0.019
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.21
T
M_CAP
Benign
0.044
D
MetaRNN
Uncertain
0.45
T
MetaSVM
Benign
-0.37
T
MutationAssessor
Benign
2.0
M
PhyloP100
0.70
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-6.1
D
REVEL
Benign
0.17
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.010
D
Polyphen
0.27
B
Vest4
0.11
MutPred
0.39
Gain of catalytic residue at P255 (P = 0.0543)
MVP
0.50
ClinPred
0.87
D
GERP RS
3.5
Varity_R
0.45
gMVP
0.21
Mutation Taster
=90/10
polymorphism

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

Other links and lift over

dbSNP: rs3733698; hg19: chr5-140502343; API