rs763579521

Variant names:

• chr10-71213008-G-A
• NM_170744.5:c.23G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-71213008-G-A
• chr10-71213008-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170744.5(UNC5B):​c.23G>A​(p.Arg8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000794 in 1,259,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: 1.30

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14365262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5B	NM_170744.5	c.23G>A	p.Arg8Gln	missense_variant	Exon 1 of 17	ENST00000335350.10	NP_734465.2
UNC5B	NM_001244889.2	c.23G>A	p.Arg8Gln	missense_variant	Exon 1 of 16		NP_001231818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5B	ENST00000335350.10	c.23G>A	p.Arg8Gln	missense_variant	Exon 1 of 17	1	NM_170744.5	ENSP00000334329.6
UNC5B	ENST00000373192.4	c.23G>A	p.Arg8Gln	missense_variant	Exon 1 of 16	1		ENSP00000362288.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.94e-7 AC: 1 AN: 1259232 Hom.: 0 Cov.: 30 AF XY: 0.00000161 AC XY: 1 AN XY: 619662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.91e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.21	N;N
REVEL	Benign	0.078
Sift	Benign	0.12	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.0030	B;B
Vest4		0.12
MutPred		0.45		Loss of MoRF binding (P = 0.0022);Loss of MoRF binding (P = 0.0022);
MVP		0.55
MPC		0.17
ClinPred		0.19	T
GERP RS		0.72
Varity_R		0.12
gMVP		0.39

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: chr10-72972765;