Genetic Variant NM_170744.5:c.71G>A (chr10-71213056-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_170744.5(UNC5B):c.71G>A(p.Ser24Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000801 in 1,248,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S24T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

UNC5B
NM_170744.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.64

Publications

0 publications found

Variant links:

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]

UNC5B links:

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ACMG classification

Classification was made for transcript

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=0.14904824).

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.71G>A	p.Ser24Asn	missense	Exon 1 of 17	NP_734465.2
	UNC5B	NM_001244889.2		c.71G>A	p.Ser24Asn	missense	Exon 1 of 16	NP_001231818.1	Q8IZJ1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UNC5B	ENST00000335350.10	TSL:1 MANE Select	c.71G>A	p.Ser24Asn	missense	Exon 1 of 17	ENSP00000334329.6	Q8IZJ1-1
UNC5B	ENST00000373192.4	TSL:1	c.71G>A	p.Ser24Asn	missense	Exon 1 of 16	ENSP00000362288.4	Q8IZJ1-2
UNC5B	ENST00000935474.1		c.71G>A	p.Ser24Asn	missense	Exon 1 of 17	ENSP00000605533.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.01e-7

AC:

AN:

1248002

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

612562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26544

American (AMR)

AF:

0.00

AC:

AN:

22426

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19456

East Asian (EAS)

AF:

0.00

AC:

AN:

30654

South Asian (SAS)

AF:

0.00

AC:

AN:

53706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4976

European-Non Finnish (NFE)

AF:

9.98e-7

AC:

AN:

1001946

Other (OTH)

AF:

0.00

AC:

AN:

49968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

4.6

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.74

REVEL

Benign

0.063

Sift

Benign

0.062

Sift4G

Benign

0.30

Polyphen

0.28

Vest4

0.27

MutPred

0.22

Loss of phosphorylation at S24 (P = 0.0384)

MVP

0.59

MPC

0.17

ClinPred

0.62

GERP RS

3.5

PromoterAI

0.024

Neutral

(source)

Varity_R

0.079

gMVP

0.27

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over