NM_001257.5:c.1126G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001257.5(CDH13):c.1126G>A(p.Ala376Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 1,613,924 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 44 hom. )

Consequence

CDH13
NM_001257.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.42

Publications

8 publications found

Variant links:

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

CDH13 links:

LOC124900603 (HGNC:):

LOC124900603 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007640034).

BP6

Variant 16-83670814-G-A is Benign according to our data. Variant chr16-83670814-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 44 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5 link	c.1126G>A	p.Ala376Thr	missense_variant	Exon 9 of 14	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6 link	c.1126G>A	p.Ala376Thr	missense_variant	Exon 9 of 14	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes

AF:

0.00506

AC:

770

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.0237

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00836

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00563

AC:

1404

AN:

249164

AF XY:

0.00581

show subpopulations

Gnomad AFR exome

AF:

0.000710

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.0197

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00237

Gnomad NFE exome

AF:

0.00843

Gnomad OTH exome

AF:

0.00727

GnomAD4 exome

AF:

0.00709

AC:

10360

AN:

1461596

Hom.:

Cov.:

AF XY:

0.00707

AC XY:

5140

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33474

American (AMR)

AF:

0.00197

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0191

AC:

500

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00262

AC:

226

AN:

86254

European-Finnish (FIN)

AF:

0.00258

AC:

138

AN:

53402

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00805

AC:

8950

AN:

1111780

Other (OTH)

AF:

0.00684

AC:

413

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

524

1047

1571

2094

2618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.00505

AC:

770

AN:

152328

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

337

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41566

American (AMR)

AF:

0.00183

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0237

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00836

AC:

569

AN:

68038

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

125

166

208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00770

Hom.:

Bravo

AF:

0.00498

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00154

AC:

ESP6500EA

AF:

0.00700

AC:

ExAC

AF:

0.00592

AC:

715

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00862

EpiControl

AF:

0.00777

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

T;.;.

Eigen

Benign

-0.051

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.0076

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.47

N;.;.

PhyloP100

3.4

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.14

.;N;N

REVEL

Benign

0.093

Sift

Benign

0.18

.;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.27

B;.;.

Vest4

0.18

MVP

0.80

MPC

0.075

ClinPred

0.017

GERP RS

5.9

Varity_R

0.12

gMVP

0.44

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over