NM_170744.5:c.424C>T

Variant names:

• chr10-71284839-C-T
• rs141063931
• NM_170744.5:c.424C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09573418).

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.424C>T	p.Arg142Cys	missense	Exon 3 of 17	NP_734465.2
	UNC5B	NM_001244889.2		c.424C>T	p.Arg142Cys	missense	Exon 3 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.424C>T	p.Arg142Cys	missense	Exon 3 of 17	ENSP00000334329.6	Q8IZJ1-1
	UNC5B	ENST00000373192.4	TSL:1	c.424C>T	p.Arg142Cys	missense	Exon 3 of 16	ENSP00000362288.4	Q8IZJ1-2
	UNC5B	ENST00000935474.1		c.424C>T	p.Arg142Cys	missense	Exon 3 of 17	ENSP00000605533.1

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152168 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000505 AC: 125 AN: 247564 AF XY: 0.000553

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 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.: 1 Cov.: 55 AF XY: 0.000829 AC XY: 602 AN XY: 725808

African (AFR) AF: 0.000209 AC: 7 AN: 33472

American (AMR) AF: 0.000291 AC: 13 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25940

East Asian (EAS) AF: 0.000731 AC: 29 AN: 39692

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86034

European-Finnish (FIN) AF: 0.0000570 AC: 3 AN: 52588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.000985 AC: 1094 AN: 1110834

Other (OTH) AF: 0.00129 AC: 78 AN: 60316

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152286 Hom.: 0 Cov.: 33 AF XY: 0.000483 AC XY: 36 AN XY: 74462

African (AFR) AF: 0.000144 AC: 6 AN: 41558

American (AMR) AF: 0.000196 AC: 3 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5154

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000912 AC: 62 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000600 Hom.: 0

Bravo AF: 0.000548

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.000544 AC: 66

Asia WGS AF: 0.00318 AC: 11 AN: 3478

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	0.19
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.5
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.63
MVP		0.61
MPC		0.57
ClinPred		0.11	T
GERP RS		5.0
Varity_R		0.48
gMVP		0.48
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs141063931; hg19: chr10-73044596; COSMIC: COSV58975969;