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GeneBe

5-176862836-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_133369.3(UNC5A):c.283G>A(p.Gly95Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,612,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

UNC5A
NM_133369.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.824
Variant links:
Genes affected
UNC5A (HGNC:12567): (unc-5 netrin receptor A) UNC5A belongs to a family of netrin-1 (MIM 601614) receptors thought to mediate the chemorepulsive effect of netrin-1 on specific axons. For more information on UNC5 proteins, see UNC5C (MIM 603610).[supplied by OMIM, Apr 2004]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, UNC5A
BP4
Computational evidence support a benign effect (MetaRNN=0.016928583).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UNC5ANM_133369.3 linkuse as main transcriptc.283G>A p.Gly95Arg missense_variant 2/15 ENST00000329542.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UNC5AENST00000329542.9 linkuse as main transcriptc.283G>A p.Gly95Arg missense_variant 2/151 NM_133369.3 Q6ZN44-1
UNC5AENST00000513890.1 linkuse as main transcriptc.214G>A p.Gly72Arg missense_variant, NMD_transcript_variant 1/91
UNC5AENST00000509580.2 linkuse as main transcriptc.283G>A p.Gly95Arg missense_variant 2/165 P1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152254
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000560
AC:
14
AN:
249870
Hom.:
0
AF XY:
0.0000591
AC XY:
8
AN XY:
135356
show subpopulations
Gnomad AFR exome
AF:
0.000372
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.0000982
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000390
AC:
57
AN:
1460612
Hom.:
0
Cov.:
32
AF XY:
0.0000317
AC XY:
23
AN XY:
726646
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.0000570
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152372
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.000385
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000102
Hom.:
0
Bravo
AF:
0.000196
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

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 submitterclinical testingAmbry GeneticsJan 05, 2022The c.283G>A (p.G95R) alteration is located in exon 2 (coding exon 2) of the UNC5A gene. This alteration results from a G to A substitution at nucleotide position 283, causing the glycine (G) at amino acid position 95 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.63
Cadd
Benign
4.3
Dann
Benign
0.91
DEOGEN2
Benign
0.032
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.19
T;T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.017
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-1.4
N;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
0.73
N;.
REVEL
Benign
0.021
Sift
Benign
0.16
T;.
Sift4G
Benign
0.28
T;.
Polyphen
0.0010
B;.
Vest4
0.095
MutPred
0.20
Loss of glycosylation at S97 (P = 0.0775);Loss of glycosylation at S97 (P = 0.0775);
MVP
0.11
MPC
0.71
ClinPred
0.021
T
GERP RS
-1.5
Varity_R
0.078
gMVP
0.30

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: rs140306147; hg19: chr5-176289837; API