NM_170744.5:c.281A>G

Variant names:

• chr10-71280022-A-G
• rs1844882296
• NM_170744.5:c.281A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170744.5(UNC5B):​c.281A>G​(p.Gln94Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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: 4.32
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14791563).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170744.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5B	NM_170744.5	MANE Select	c.281A>G	p.Gln94Arg	missense	Exon 2 of 17	NP_734465.2
	UNC5B	NM_001244889.2		c.281A>G	p.Gln94Arg	missense	Exon 2 of 16	NP_001231818.1	Q8IZJ1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5B	ENST00000335350.10	TSL:1 MANE Select	c.281A>G	p.Gln94Arg	missense	Exon 2 of 17	ENSP00000334329.6	Q8IZJ1-1
	UNC5B	ENST00000373192.4	TSL:1	c.281A>G	p.Gln94Arg	missense	Exon 2 of 16	ENSP00000362288.4	Q8IZJ1-2
	UNC5B	ENST00000935474.1		c.281A>G	p.Gln94Arg	missense	Exon 2 of 17	ENSP00000605533.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.35	N
PhyloP100		4.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.030
Sift	Benign	0.12	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.25		Loss of disorder (P = 0.168)
MVP		0.67
MPC		0.16
ClinPred		0.54	D
GERP RS		4.5
Varity_R		0.11
gMVP		0.22
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1844882296; hg19: chr10-73039779;