7-105996344-C-T
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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
NM_152750.5 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 1.13
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]
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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 |
---|---|---|---|---|---|---|---|---|
CDHR3 | NM_152750.5 | c.703C>T | p.Arg235Cys | missense_variant | 6/19 | ENST00000317716.14 | NP_689963.2 | |
CDHR3 | NM_001301161.2 | c.439C>T | p.Arg147Cys | missense_variant | 5/18 | NP_001288090.1 | ||
LOC107986833 | XR_001745316.2 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDHR3 | ENST00000317716.14 | c.703C>T | p.Arg235Cys | missense_variant | 6/19 | 1 | NM_152750.5 | ENSP00000325954 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152198Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000420 AC: 10AN: 237966Hom.: 0 AF XY: 0.0000619 AC XY: 8AN XY: 129168
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GnomAD4 exome AF: 0.0000341 AC: 49AN: 1438112Hom.: 0 Cov.: 29 AF XY: 0.0000295 AC XY: 21AN XY: 710902
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74362
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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 submitter | clinical testing | Ambry Genetics | Jan 17, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Loss of phosphorylation at S238 (P = 0.0509);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at