rs193921054

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_001793.6(CDH3):c.235G>A(p.Glu79Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,612,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CDH3
NM_001793.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.326

Publications

2 publications found

Variant links:

Genes affected

CDH3 (HGNC:1762): (cadherin 3) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS). [provided by RefSeq, Nov 2015]

CDH3 Gene-Disease associations (from GenCC):

EEM syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen
congenital hypotrichosis with juvenile macular dystrophy
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

CDH3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.021563888).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000118 (18/152300) while in subpopulation AFR AF = 0.000385 (16/41552). AF 95% confidence interval is 0.000241. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001793.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH3	NM_001793.6	MANE Select	c.235G>A	p.Glu79Lys	missense	Exon 3 of 16	NP_001784.2
CDH3	NM_001317195.3		c.235G>A	p.Glu79Lys	missense	Exon 3 of 16	NP_001304124.1	P22223-2
CDH3	NM_001317196.2		c.70G>A	p.Glu24Lys	missense	Exon 2 of 15	NP_001304125.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH3	ENST00000264012.9	TSL:1 MANE Select	c.235G>A	p.Glu79Lys	missense	Exon 3 of 16	ENSP00000264012.4	P22223-1
CDH3	ENST00000429102.6	TSL:1	c.235G>A	p.Glu79Lys	missense	Exon 3 of 16	ENSP00000398485.2	P22223-2
CDH3	ENST00000914963.1		c.235G>A	p.Glu79Lys	missense	Exon 3 of 16	ENSP00000585022.1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000835

AC:

AN:

251454

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1460332

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

726590

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33456

American (AMR)

AF:

0.000134

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

1110584

Other (OTH)

AF:

0.0000829

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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

AF:

0.000118

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41552

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000661

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.5

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.058

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.63

M_CAP

Benign

0.014

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

0.33

PrimateAI

Benign

0.22

PROVEAN

Benign

0.17

REVEL

Benign

0.025

Sift

Benign

0.065

Sift4G

Benign

0.84

Polyphen

0.20

Vest4

0.11

MVP

0.43

MPC

0.23

ClinPred

0.0051

GERP RS

-1.5

Varity_R

0.038

gMVP

0.54

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over