Variant 7-106012871-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152750.5(CDHR3):c.1064C>T(p.Pro355Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000524 in 1,603,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P355S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

CDHR3
NM_152750.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.399

Variant links:

Genes affected

CDHR3 (HGNC:26308): (cadherin related family member 3) Predicted to enable cadherin binding activity and calcium ion binding activity. Predicted to be involved in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; cell morphogenesis; and cell-cell junction organization. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CDHR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031600177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR3	NM_152750.5 linkuse as main transcript	c.1064C>T	p.Pro355Leu	missense_variant	9/19	ENST00000317716.14
CDHR3	NM_001301161.2 linkuse as main transcript	c.800C>T	p.Pro267Leu	missense_variant	8/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR3	ENST00000317716.14 linkuse as main transcript	c.1064C>T	p.Pro355Leu	missense_variant	9/19	1	NM_152750.5	P1	Q6ZTQ4-1

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

239054

Hom.:

AF XY:

0.000108

AC XY:

AN XY:

129618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000933

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00104

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000482

AC:

AN:

1451160

Hom.:

Cov.:

AF XY:

0.0000485

AC XY:

AN XY:

721472

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000706

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000922

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000122

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Susceptibility to nonsyndromic otitis media

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Santos-Cortez Lab, University of Colorado School of Medicine

Feb 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Benign

0.72

DEOGEN2

Benign

0.052

T;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

2.0

M;.;.

MutationTaster

Benign

0.84

D;D;D;D;D

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Benign

0.063

Sift

Benign

0.075

T;T;D

Sift4G

Benign

0.14

T;T;D

Polyphen

0.34

B;.;.

Vest4

0.23

MutPred

0.46

Loss of phosphorylation at T358 (P = 0.1008);.;.;

MVP

0.46

MPC

0.035

ClinPred

0.035

GERP RS

3.5

Varity_R

0.079

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over