10-71213040-T-G

Variant names:

• chr10-71213040-T-G
• rs1017635371
• NM_170744.5:c.55T>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.55T>G​(p.Trp19Gly) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W19R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: UNC5B NM_170744.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24853727).

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>G	p.Trp19Gly	missense	Exon 1 of 17	NP_734465.2
	UNC5B	NM_001244889.2		c.55T>G	p.Trp19Gly	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>G	p.Trp19Gly	missense	Exon 1 of 17	ENSP00000334329.6	Q8IZJ1-1
	UNC5B	ENST00000373192.4	TSL:1	c.55T>G	p.Trp19Gly	missense	Exon 1 of 16	ENSP00000362288.4	Q8IZJ1-2
	UNC5B	ENST00000935474.1		c.55T>G	p.Trp19Gly	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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000373 AC: 1 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: 0.00 AC: 0 AN: 1010578

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Benign	0.87
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.0015
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.17
Sift	Benign	0.26	T
Sift4G	Benign	0.24	T
Polyphen		0.60	P
Vest4		0.47
MutPred		0.52		Gain of disorder (P = 3e-04)
MVP		0.48
MPC		0.27
ClinPred		0.33	T
GERP RS		4.4
PromoterAI		0.0032	Neutral
Varity_R		0.49
gMVP		0.41
Mutation Taster		=85/15	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;