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GeneBe

4-95170270-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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.44
Variant links:
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
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.43 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UNC5CNM_003728.4 linkuse as main transcriptc.2514G>A p.Gly838= synonymous_variant 15/16 ENST00000453304.6
UNC5CXM_005263321.4 linkuse as main transcriptc.2571G>A p.Gly857= synonymous_variant 16/17
UNC5CXM_047416345.1 linkuse as main transcriptc.1470G>A p.Gly490= synonymous_variant 17/18
UNC5CXM_047416346.1 linkuse as main transcriptc.1470G>A p.Gly490= synonymous_variant 18/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UNC5CENST00000453304.6 linkuse as main transcriptc.2514G>A p.Gly838= synonymous_variant 15/161 NM_003728.4 P1O95185-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000782
AC:
119
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000387
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00235
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00122
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000871
AC:
219
AN:
251434
Hom.:
1
AF XY:
0.000846
AC XY:
115
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00148
Gnomad NFE exome
AF:
0.00153
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.00113
AC:
1654
AN:
1461884
Hom.:
0
Cov.:
34
AF XY:
0.00105
AC XY:
765
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00122
Gnomad4 NFE exome
AF:
0.00137
Gnomad4 OTH exome
AF:
0.000878
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000782
AC:
119
AN:
152234
Hom.:
0
Cov.:
32
AF XY:
0.000873
AC XY:
65
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000388
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00235
Gnomad4 NFE
AF:
0.00122
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000915
Hom.:
0
Bravo
AF:
0.000589
EpiCase
AF:
0.000927
EpiControl
AF:
0.00101

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 submitterclinical testingPreventionGenetics, part of Exact SciencesApr 09, 2019This 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 submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2022UNC5C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
0.26
Dann
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146932015; hg19: chr4-96091421; API