Variant 10-71284839-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_170744.5(UNC5B):c.424C>T(p.Arg142Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00081 in 1,611,518 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 1 hom. )

Consequence

UNC5B
NM_170744.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Variant links:

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]

UNC5B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09573418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5B	NM_170744.5 linkuse as main transcript	c.424C>T	p.Arg142Cys	missense_variant	3/17	ENST00000335350.10
UNC5B	NM_001244889.2 linkuse as main transcript	c.424C>T	p.Arg142Cys	missense_variant	3/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5B	ENST00000335350.10 linkuse as main transcript	c.424C>T	p.Arg142Cys	missense_variant	3/17	1	NM_170744.5	P4	Q8IZJ1-1
UNC5B	ENST00000373192.4 linkuse as main transcript	c.424C>T	p.Arg142Cys	missense_variant	3/16	1		A1	Q8IZJ1-2

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000505

AC:

125

AN:

247564

Hom.:

AF XY:

0.000553

AC XY:

AN XY:

133812

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.0000479

Gnomad NFE exome

AF:

0.000716

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000844

AC:

1231

AN:

1459232

Hom.:

Cov.:

AF XY:

0.000829

AC XY:

602

AN XY:

725808

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.000731

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.0000570

Gnomad4 NFE exome

AF:

0.000985

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.000486

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000912

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000668

Hom.:

Bravo

AF:

0.000548

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000544

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

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

Jun 06, 2023

The c.424C>T (p.R142C) alteration is located in exon 3 (coding exon 3) of the UNC5B gene. This alteration results from a C to T substitution at nucleotide position 424, causing the arginine (R) at amino acid position 142 to be replaced by a cysteine (C). 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

0.19

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.53

D;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.80

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-6.3

D;D

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.99

D;D

Vest4

0.63

MVP

0.61

MPC

0.57

ClinPred

0.11

GERP RS

5.0

Varity_R

0.48

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over