chr10-71284839-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_170744.5(UNC5B):c.424C>T(p.Arg142Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00081 in 1,611,518 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00084 ( 1 hom. )
Consequence
UNC5B
NM_170744.5 missense
NM_170744.5 missense
Scores
5
5
9
Clinical Significance
Conservation
PhyloP100: 2.52
Genes affected
UNC5B (HGNC:12568): (unc-5 netrin receptor B) This gene encodes a member of the netrin family of receptors. This particular protein mediates the repulsive effect of netrin-1 and is a vascular netrin receptor. This encoded protein is also in a group of proteins called dependence receptors (DpRs) which are involved in pro- and anti-apoptotic processes. Many DpRs are involved in embryogenesis and in cancer progression. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09573418).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC5B | NM_170744.5 | c.424C>T | p.Arg142Cys | missense_variant | 3/17 | ENST00000335350.10 | |
UNC5B | NM_001244889.2 | c.424C>T | p.Arg142Cys | missense_variant | 3/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC5B | ENST00000335350.10 | c.424C>T | p.Arg142Cys | missense_variant | 3/17 | 1 | NM_170744.5 | P4 | |
UNC5B | ENST00000373192.4 | c.424C>T | p.Arg142Cys | missense_variant | 3/16 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000486 AC: 74AN: 152168Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000505 AC: 125AN: 247564Hom.: 0 AF XY: 0.000553 AC XY: 74AN XY: 133812
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GnomAD4 exome AF: 0.000844 AC: 1231AN: 1459232Hom.: 1 Cov.: 55 AF XY: 0.000829 AC XY: 602AN XY: 725808
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GnomAD4 genome AF: 0.000486 AC: 74AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.000483 AC XY: 36AN XY: 74462
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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 | Jun 06, 2023 | The c.424C>T (p.R142C) alteration is located in exon 3 (coding exon 3) of the UNC5B gene. This alteration results from a C to T substitution at nucleotide position 424, causing the arginine (R) at amino acid position 142 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
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
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