Variant chr10-71213040-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_170744.5(UNC5B):c.55T>A(p.Trp19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000791 in 1,264,034 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

UNC5B
NM_170744.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3369749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5B	NM_170744.5 link	c.55T>A	p.Trp19Arg	missense_variant	1/17	ENST00000335350.10	NP_734465.2	Q8IZJ1-1
UNC5B	NM_001244889.2 link	c.55T>A	p.Trp19Arg	missense_variant	1/16		NP_001231818.1	Q8IZJ1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5B	ENST00000335350.10 link	c.55T>A	p.Trp19Arg	missense_variant	1/17	1	NM_170744.5	ENSP00000334329.6		Q8IZJ1-1
UNC5B	ENST00000373192.4 link	c.55T>A	p.Trp19Arg	missense_variant	1/16	1		ENSP00000362288.4		Q8IZJ1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.91e-7

AC:

AN:

1264034

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

622550

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.90e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 13, 2021

The c.55T>A (p.W19R) alteration is located in exon 1 (coding exon 1) of the UNC5B gene. This alteration results from a T to A substitution at nucleotide position 55, causing the tryptophan (W) at amino acid position 19 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

0.21

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.35

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.90

L;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.21

Sift

Benign

0.28

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.94

P;D

Vest4

0.33

MutPred

0.49

Gain of disorder (P = 0);Gain of disorder (P = 0);

MVP

0.75

MPC

0.28

ClinPred

0.58

GERP RS

4.4

Varity_R

0.31

gMVP

0.46

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.

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