chr4-95170270-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_003728.4(UNC5C):c.2514G>A(p.Gly838=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 0 hom. )
Consequence
UNC5C
NM_003728.4 synonymous
NM_003728.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.44
Genes affected
UNC5C (HGNC:12569): (unc-5 netrin receptor C) This gene product belongs to the UNC-5 family of netrin receptors. Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional proteins that act as attractants for some cell types and as repellents for others, and these opposite actions are thought to be mediated by two classes of receptors. The UNC-5 family of receptors mediate the repellent response to netrin; they are transmembrane proteins containing 2 immunoglobulin (Ig)-like domains and 2 type I thrombospondin motifs in the extracellular region. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
Variant 4-95170270-C-T is Benign according to our data. Variant chr4-95170270-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.43 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC5C | NM_003728.4 | c.2514G>A | p.Gly838= | synonymous_variant | 15/16 | ENST00000453304.6 | |
UNC5C | XM_005263321.4 | c.2571G>A | p.Gly857= | synonymous_variant | 16/17 | ||
UNC5C | XM_047416345.1 | c.1470G>A | p.Gly490= | synonymous_variant | 17/18 | ||
UNC5C | XM_047416346.1 | c.1470G>A | p.Gly490= | synonymous_variant | 18/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC5C | ENST00000453304.6 | c.2514G>A | p.Gly838= | synonymous_variant | 15/16 | 1 | NM_003728.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000782 AC: 119AN: 152116Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000871 AC: 219AN: 251434Hom.: 1 AF XY: 0.000846 AC XY: 115AN XY: 135890
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GnomAD4 exome AF: 0.00113 AC: 1654AN: 1461884Hom.: 0 Cov.: 34 AF XY: 0.00105 AC XY: 765AN XY: 727240
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GnomAD4 genome ? AF: 0.000782 AC: 119AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.000873 AC XY: 65AN XY: 74426
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
UNC5C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 09, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2022 | UNC5C: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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