10-71280031-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_170744.5(UNC5B):c.290T>C(p.Leu97Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UNC5B NM_170744.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5B	NM_170744.5	c.290T>C	p.Leu97Pro	missense_variant	2/17	ENST00000335350.10
UNC5B	NM_001244889.2	c.290T>C	p.Leu97Pro	missense_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5B	ENST00000335350.10	c.290T>C	p.Leu97Pro	missense_variant	2/17	1	NM_170744.5	P4
UNC5B	ENST00000373192.4	c.290T>C	p.Leu97Pro	missense_variant	2/16	1		A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.290T>C (p.L97P) alteration is located in exon 2 (coding exon 2) of the UNC5B gene. This alteration results from a T to C substitution at nucleotide position 290, causing the leucine (L) at amino acid position 97 to be replaced by a proline (P). 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	0.17
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.16
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.94	P;P
Vest4		0.83
MutPred		0.45		Gain of disorder (P = 0.0318);Gain of disorder (P = 0.0318);
MVP		0.62
MPC		0.47
ClinPred		0.97	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.54
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-73039788;