NM_170744.5:c.55T>A

Variant names:

• chr10-71213040-T-A
• rs1017635371
• NM_170744.5:c.55T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3369749).

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.55T>A	p.Trp19Arg	missense	Exon 1 of 17	NP_734465.2
	UNC5B	NM_001244889.2		c.55T>A	p.Trp19Arg	missense	Exon 1 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.55T>A	p.Trp19Arg	missense	Exon 1 of 17	ENSP00000334329.6	Q8IZJ1-1
	UNC5B	ENST00000373192.4	TSL:1	c.55T>A	p.Trp19Arg	missense	Exon 1 of 16	ENSP00000362288.4	Q8IZJ1-2
	UNC5B	ENST00000935474.1		c.55T>A	p.Trp19Arg	missense	Exon 1 of 17	ENSP00000605533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.91e-7 AC: 1 AN: 1264034 Hom.: 0 Cov.: 30 AF XY: 0.00000161 AC XY: 1 AN XY: 622550

African (AFR) AF: 0.00 AC: 0 AN: 26792

American (AMR) AF: 0.00 AC: 0 AN: 24462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20132

East Asian (EAS) AF: 0.00 AC: 0 AN: 30904

South Asian (SAS) AF: 0.00 AC: 0 AN: 56490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4988

European-Non Finnish (NFE) AF: 9.90e-7 AC: 1 AN: 1010578

Other (OTH) AF: 0.00 AC: 0 AN: 50548

GnomAD4 genome Cov.: 32

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	0.21
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.21
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Polyphen		0.94	P
Vest4		0.33
MutPred		0.49		Gain of disorder (P = 0)
MVP		0.75
MPC		0.28
ClinPred		0.58	D
GERP RS		4.4
PromoterAI		-0.044	Neutral
Varity_R		0.31
gMVP		0.46
Mutation Taster		=86/14	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: rs1017635371; hg19: chr10-72972797;