Genetic Variant NM_032420.5:c.3545C>T (chr5-141854211-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032420.5(PCDH1):c.3545C>T(p.Thr1182Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,458,620 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 1 hom. )

Consequence

PCDH1
NM_032420.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96

Publications

0 publications found

Variant links:

Genes affected

PCDH1 (HGNC:8655): (protocadherin 1) This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene. [provided by RefSeq, Jul 2008]

PCDH1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04336509).

BS2

High AC in GnomAdExome4 at 27 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032420.5. 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
	PCDH1	NM_032420.5	MANE Select	c.3545C>T	p.Thr1182Met	missense	Exon 5 of 5	NP_115796.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH1	ENST00000287008.8	TSL:5 MANE Select	c.3545C>T	p.Thr1182Met	missense	Exon 5 of 5	ENSP00000287008.3	Q08174-2
	PCDH1	ENST00000503492.5	TSL:5	c.*239C>T		3_prime_UTR	Exon 5 of 5	ENSP00000424667.1	D6RAX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000533

AC:

AN:

244116

AF XY:

0.0000378

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000364

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1458620

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

725260

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33426

American (AMR)

AF:

0.0000450

AC:

AN:

44428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26010

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.000140

AC:

AN:

85988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53128

Middle Eastern (MID)

AF:

0.000525

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00000811

AC:

AN:

1110122

Other (OTH)

AF:

0.00

AC:

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000659

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

0.064

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.62

CADD

Uncertain

(source)

DANN

Benign

0.96

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.75

M_CAP

Benign

0.014

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.1

PhyloP100

3.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.45

REVEL

Benign

0.14

Sift

Benign

0.19

Sift4G

Benign

0.32

Polyphen

0.0080

Vest4

0.095

MutPred

0.21

Loss of glycosylation at T1182 (P = 0.0204)

MVP

0.068

MPC

0.46

ClinPred

0.099

GERP RS

3.6

gMVP

0.31

Mutation Taster

=96/4

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