10-71286824-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_170744.5(UNC5B):c.688A>T(p.Ile230Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
UNC5B
NM_170744.5 missense
NM_170744.5 missense
Scores
2
13
4
Clinical Significance
Conservation
PhyloP100: 5.25
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.785
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC5B | NM_170744.5 | c.688A>T | p.Ile230Phe | missense_variant | 5/17 | ENST00000335350.10 | |
UNC5B | NM_001244889.2 | c.688A>T | p.Ile230Phe | missense_variant | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC5B | ENST00000335350.10 | c.688A>T | p.Ile230Phe | missense_variant | 5/17 | 1 | NM_170744.5 | P4 | |
UNC5B | ENST00000373192.4 | c.688A>T | p.Ile230Phe | missense_variant | 5/16 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152098Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251396Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135872
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727238
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GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152098Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74306
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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 | Dec 02, 2022 | The c.688A>T (p.I230F) alteration is located in exon 5 (coding exon 5) of the UNC5B gene. This alteration results from a A to T substitution at nucleotide position 688, causing the isoleucine (I) at amino acid position 230 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
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