Variant 5-141178357-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_019120.5(PCDHB8):c.323A>C(p.Gln108Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 145,962 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000045 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCDHB8
NM_019120.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.26

Variant links:

Genes affected

PCDHB8 (HGNC:8693): (protocadherin beta 8) 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]

PCDHB8 links:

PCDHB@ (HGNC:8679):

PCDHB@ links:

ENSG00000279472 (HGNC:):

ENSG00000279472 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDHB8	NM_019120.5 link	c.323A>C	p.Gln108Pro	missense_variant	1/1	ENST00000239444.4	NP_061993.3	Q9UN66
PCDHB@		n.141178357A>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCDHB8	ENST00000239444.4 link	c.323A>C	p.Gln108Pro	missense_variant	1/1	6	NM_019120.5	ENSP00000239444.2	Q9UN66
ENSG00000279472	ENST00000623995.1 link	n.221+288A>C		intron_variant		4
ENSG00000280029	ENST00000624192.1 link	n.73-41174T>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

145852

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:

0.000463

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000775

AC:

AN:

245260

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

133668

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:

0.000623

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000449

AC:

AN:

1403492

Hom.:

Cov.:

AF XY:

0.0000685

AC XY:

AN XY:

700962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000675

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000861

GnomAD4 genome

AF:

0.0000137

AC:

AN:

145962

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

71020

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000464

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000746

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

Jun 05, 2023

The c.323A>C (p.Q108P) alteration is located in exon 1 (coding exon 1) of the PCDHB8 gene. This alteration results from a A to C substitution at nucleotide position 323, causing the glutamine (Q) at amino acid position 108 to be replaced by a proline (P). 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Pathogenic

0.76

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

-0.19

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Vest4

0.50

MutPred

0.58

Gain of loop (P = 0.2754);

MVP

0.76

MPC

1.0

ClinPred

0.78

GERP RS

4.3

gMVP

0.64

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

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