7-105996344-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152750.5(CDHR3):​c.703C>T​(p.Arg235Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000371 in 1,590,310 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CDHR3
NM_152750.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13
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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDHR3NM_152750.5 linkuse as main transcriptc.703C>T p.Arg235Cys missense_variant 6/19 ENST00000317716.14 NP_689963.2
CDHR3NM_001301161.2 linkuse as main transcriptc.439C>T p.Arg147Cys missense_variant 5/18 NP_001288090.1
LOC107986833XR_001745316.2 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDHR3ENST00000317716.14 linkuse as main transcriptc.703C>T p.Arg235Cys missense_variant 6/191 NM_152750.5 ENSP00000325954 P1Q6ZTQ4-1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000420
AC:
10
AN:
237966
Hom.:
0
AF XY:
0.0000619
AC XY:
8
AN XY:
129168
show subpopulations
Gnomad AFR exome
AF:
0.000139
Gnomad AMR exome
AF:
0.0000298
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000343
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000559
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000341
AC:
49
AN:
1438112
Hom.:
0
Cov.:
29
AF XY:
0.0000295
AC XY:
21
AN XY:
710902
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.0000228
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000257
Gnomad4 SAS exome
AF:
0.0000236
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000311
Gnomad4 OTH exome
AF:
0.0000337
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000568
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 17, 2023The c.703C>T (p.R235C) alteration is located in exon 6 (coding exon 6) of the CDHR3 gene. This alteration results from a C to T substitution at nucleotide position 703, causing the arginine (R) at amino acid position 235 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;T
Eigen
Benign
0.042
Eigen_PC
Benign
-0.013
FATHMM_MKL
Benign
0.093
N
LIST_S2
Benign
0.85
D;D
M_CAP
Benign
0.0094
T
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Benign
-0.87
T
MutationAssessor
Pathogenic
2.9
M;.
MutationTaster
Benign
0.83
D;N;N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.14
Sift
Benign
0.17
T;T
Sift4G
Benign
0.062
T;T
Polyphen
0.98
D;.
Vest4
0.58
MutPred
0.52
Loss of phosphorylation at S238 (P = 0.0509);.;
MVP
0.44
MPC
0.16
ClinPred
0.28
T
GERP RS
4.3
Varity_R
0.10
gMVP
0.33

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.

Other links and lift over

dbSNP: rs201595088; hg19: chr7-105636790; API