Genetic Variant NM_032961.3:c.677C>T (chr4-133150817-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_032961.3(PCDH10):c.677C>T(p.Pro226Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,436,228 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P226T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PCDH10
NM_032961.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

Publications

0 publications found

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:

PCDH10-DT (HGNC:53036): (PCDH10 divergent transcript)

PCDH10-DT 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=0.1532107).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032961.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH10	NM_032961.3	MANE Select	c.677C>T	p.Pro226Leu	missense	Exon 1 of 5	NP_116586.1	Q9P2E7-1
	PCDH10	NM_020815.3		c.677C>T	p.Pro226Leu	missense	Exon 1 of 1	NP_065866.1	Q9P2E7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCDH10	ENST00000264360.7	TSL:1 MANE Select	c.677C>T	p.Pro226Leu	missense	Exon 1 of 5	ENSP00000264360.4	Q9P2E7-1
PCDH10	ENST00000618019.1	TSL:6	c.677C>T	p.Pro226Leu	missense	Exon 1 of 1	ENSP00000480512.1	Q9P2E7-2
PCDH10-DT	ENST00000732819.1		n.219+34G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000873

AC:

AN:

229210

AF XY:

0.00000810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000946

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1436228

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712048

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33214

American (AMR)

AF:

0.00

AC:

AN:

43596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24286

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39534

South Asian (SAS)

AF:

0.00

AC:

AN:

82580

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1100922

Other (OTH)

AF:

0.00

AC:

AN:

59442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.013

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.11

PhyloP100

3.9

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

REVEL

Benign

0.033

Sift

Pathogenic

0.0

Sift4G

Benign

0.063

Polyphen

0.0010

Vest4

0.38

MutPred

0.23

Gain of stability (P = 0.0053)

MVP

0.29

ClinPred

0.36

GERP RS

3.7

Varity_R

0.42

gMVP

0.20

Mutation Taster

=87/13

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over