rs1396101057

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152750.5(CDHR3):​c.280T>A​(p.Phe94Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. F94V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CDHR3
NM_152750.5 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.13

Publications

0 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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28806782).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDHR3NM_152750.5 linkc.280T>A p.Phe94Ile missense_variant Exon 3 of 19 ENST00000317716.14 NP_689963.2 Q6ZTQ4-1
CDHR3NM_001301161.2 linkc.16T>A p.Phe6Ile missense_variant Exon 2 of 18 NP_001288090.1 Q6ZTQ4E7EQG5B7Z8X2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDHR3ENST00000317716.14 linkc.280T>A p.Phe94Ile missense_variant Exon 3 of 19 1 NM_152750.5 ENSP00000325954.9 Q6ZTQ4-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457680
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
724610
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33444
American (AMR)
AF:
0.0000227
AC:
1
AN:
44088
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26000
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39648
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85186
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53242
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110046
Other (OTH)
AF:
0.00
AC:
0
AN:
60258
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Uncertain
0.026
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.014
T;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Benign
-0.59
T
MutationAssessor
Uncertain
2.6
M;.
PhyloP100
5.1
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.16
Sift
Benign
0.031
D;T
Sift4G
Uncertain
0.0080
D;D
Polyphen
1.0
D;.
Vest4
0.32
MutPred
0.48
Gain of relative solvent accessibility (P = 0.1571);.;
MVP
0.61
MPC
0.29
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.61
gMVP
0.57
Mutation Taster
=26/74
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1396101057; hg19: chr7-105621444; API