NM_152750.5:c.497G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152750.5(CDHR3):​c.497G>T​(p.Arg166Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R166Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CDHR3
NM_152750.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

1 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDHR3NM_152750.5 linkc.497G>T p.Arg166Leu missense_variant Exon 4 of 19 ENST00000317716.14 NP_689963.2 Q6ZTQ4-1
CDHR3NM_001301161.2 linkc.233G>T p.Arg78Leu missense_variant Exon 3 of 18 NP_001288090.1 Q6ZTQ4E7EQG5B7Z8X2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDHR3ENST00000317716.14 linkc.497G>T p.Arg166Leu missense_variant Exon 4 of 19 1 NM_152750.5 ENSP00000325954.9 Q6ZTQ4-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74468
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41558
American (AMR)
AF:
0.00
AC:
0
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68018
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
0.10
DANN
Benign
0.65
DEOGEN2
Benign
0.0030
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;.
PhyloP100
-1.8
PrimateAI
Benign
0.18
T
PROVEAN
Benign
-0.54
N;N
REVEL
Benign
0.086
Sift
Benign
0.43
T;T
Sift4G
Benign
0.17
T;T
Polyphen
0.0
B;.
Vest4
0.46
MutPred
0.36
Loss of disorder (P = 0.0537);.;
MVP
0.10
MPC
0.040
ClinPred
0.029
T
GERP RS
-3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.039
gMVP
0.22
Mutation Taster
=73/27
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.25
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.25
Position offset: 16

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

Publications

Other links and lift over

dbSNP: rs144538079; hg19: chr7-105624719; API