chr4-95169258-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_003728.4(UNC5C):c.2772C>T(p.Ser924=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,614,116 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 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000081 ( 0 hom. )
Consequence
UNC5C
NM_003728.4 synonymous
NM_003728.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.80
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 4-95169258-G-A is Benign according to our data. Variant chr4-95169258-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3048687.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.8 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC5C | NM_003728.4 | c.2772C>T | p.Ser924= | synonymous_variant | 16/16 | ENST00000453304.6 | |
UNC5C | XM_005263321.4 | c.2829C>T | p.Ser943= | synonymous_variant | 17/17 | ||
UNC5C | XM_047416345.1 | c.1728C>T | p.Ser576= | synonymous_variant | 18/18 | ||
UNC5C | XM_047416346.1 | c.1728C>T | p.Ser576= | synonymous_variant | 19/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC5C | ENST00000453304.6 | c.2772C>T | p.Ser924= | synonymous_variant | 16/16 | 1 | NM_003728.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152116Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251312Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135850
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GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461882Hom.: 0 Cov.: 30 AF XY: 0.0000839 AC XY: 61AN XY: 727240
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74440
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
UNC5C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 02, 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). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at