Genetic Variant NM_001793.6:c.813C>A (chr16-68679920-C-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001793.6(CDH3):c.813C>A(p.Thr271Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 1,613,428 control chromosomes in the GnomAD database, including 307,510 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 29975 hom., cov: 31)

Exomes 𝑓: 0.61 ( 277535 hom. )

Consequence

CDH3
NM_001793.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.67

Publications

33 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-68679920-C-A is Benign according to our data. Variant chr16-68679920-C-A is described in ClinVar as Benign. ClinVar VariationId is 320230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

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.813C>A	p.Thr271Thr	synonymous	Exon 7 of 16	NP_001784.2
CDH3	NM_001317195.3		c.813C>A	p.Thr271Thr	synonymous	Exon 7 of 16	NP_001304124.1	P22223-2
CDH3	NM_001317196.2		c.648C>A	p.Thr216Thr	synonymous	Exon 6 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.813C>A	p.Thr271Thr	synonymous	Exon 7 of 16	ENSP00000264012.4	P22223-1
CDH3	ENST00000429102.6	TSL:1	c.813C>A	p.Thr271Thr	synonymous	Exon 7 of 16	ENSP00000398485.2	P22223-2
CDH3	ENST00000914963.1		c.813C>A	p.Thr271Thr	synonymous	Exon 7 of 16	ENSP00000585022.1

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95084

AN:

151872

Hom.:

29945

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.717

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.608

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.627

Gnomad OTH

AF:

0.619

GnomAD2 exomes

AF:

0.589

AC:

148079

AN:

251444

AF XY:

0.590

show subpopulations

Gnomad AFR exome

AF:

0.675

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.579

Gnomad EAS exome

AF:

0.608

Gnomad FIN exome

AF:

0.603

Gnomad NFE exome

AF:

0.620

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.615

AC:

898318

AN:

1461438

Hom.:

277535

Cov.:

AF XY:

0.612

AC XY:

445283

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.669

AC:

22392

AN:

33472

American (AMR)

AF:

0.483

AC:

21620

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

15156

AN:

26136

East Asian (EAS)

AF:

0.632

AC:

25098

AN:

39684

South Asian (SAS)

AF:

0.542

AC:

46750

AN:

86250

European-Finnish (FIN)

AF:

0.611

AC:

32658

AN:

53412

Middle Eastern (MID)

AF:

0.552

AC:

3183

AN:

5764

European-Non Finnish (NFE)

AF:

0.625

AC:

694513

AN:

1111614

Other (OTH)

AF:

0.612

AC:

36948

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

19470

38940

58409

77879

97349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18552

37104

55656

74208

92760

<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:

0.626

AC:

95170

AN:

151990

Hom.:

29975

Cov.:

AF XY:

0.621

AC XY:

46129

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.673

AC:

27897

AN:

41436

American (AMR)

AF:

0.541

AC:

8254

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

1980

AN:

3468

East Asian (EAS)

AF:

0.625

AC:

3220

AN:

5148

South Asian (SAS)

AF:

0.544

AC:

2618

AN:

4810

European-Finnish (FIN)

AF:

0.608

AC:

6428

AN:

10574

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.627

AC:

42623

AN:

67968

Other (OTH)

AF:

0.620

AC:

1308

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1790

3580

5371

7161

8951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.613

Hom.:

37928

Bravo

AF:

0.623

EpiCase

AF:

0.621

EpiControl

AF:

0.618

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

EEM syndrome (2)

Congenital hypotrichosis with juvenile macular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.44

(source)

DANN

Benign

0.28

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(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