Variant 4-133150891-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032961.3(PCDH10):c.751G>C(p.Asp251His) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,611,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PCDH10
NM_032961.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.74

Variant links:

Genes affected

PCDH10 (HGNC:13404): (protocadherin 10) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This family member contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein is a cadherin-related neuronal receptor thought to function in the establishment of specific cell-cell connections in the brain. This gene plays a role in inhibiting cancer cell motility and cell migration. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

PCDH10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3630149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PCDH10	NM_032961.3 linkuse as main transcript	c.751G>C	p.Asp251His	missense_variant	1/5	ENST00000264360.7	NP_116586.1
PCDH10	NM_020815.3 linkuse as main transcript	c.751G>C	p.Asp251His	missense_variant	1/1		NP_065866.1
PCDH10	XM_011532150.2 linkuse as main transcript	c.751G>C	p.Asp251His	missense_variant	1/5		XP_011530452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH10	ENST00000264360.7 linkuse as main transcript	c.751G>C	p.Asp251His	missense_variant	1/5	1	NM_032961.3	ENSP00000264360	P1	Q9P2E7-1
PCDH10	ENST00000618019.1 linkuse as main transcript	c.751G>C	p.Asp251His	missense_variant	1/1			ENSP00000480512		Q9P2E7-2

Frequencies

GnomAD3 genomes

AF:

0.0000463

AC:

AN:

151346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249516

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134888

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460476

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000463

AC:

AN:

151346

Hom.:

Cov.:

AF XY:

0.0000677

AC XY:

AN XY:

73902

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000102

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

Jan 02, 2024

The c.751G>C (p.D251H) alteration is located in exon 1 (coding exon 1) of the PCDH10 gene. This alteration results from a G to C substitution at nucleotide position 751, causing the aspartic acid (D) at amino acid position 251 to be replaced by a histidine (H). 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

0.28

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

.;D

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.6

.;D

REVEL

Benign

0.23

Sift

Uncertain

0.027

.;D

Sift4G

Uncertain

0.053

T;D

Polyphen

0.90

.;P

Vest4

0.29

MutPred

0.24

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.52

ClinPred

0.95

GERP RS

4.4

Varity_R

0.41

gMVP

0.43

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