Genetic Variant UNC119B:p.Thr58Met (chr12-120710647-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080533.3(UNC119B):c.173C>T(p.Thr58Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,448,444 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

UNC119B
NM_001080533.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Publications

0 publications found

Variant links:

Genes affected

UNC119B (HGNC:16488): (unc-119 lipid binding chaperone B) Enables lipid binding activity. Involved in cilium assembly and lipoprotein transport. Located in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

UNC119B links:

ENSG00000294027 (HGNC:):

ENSG00000294027 links:

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ACMG classification

Classification was made for transcript

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=0.29040125).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080533.3. 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
	UNC119B	NM_001080533.3	MANE Select	c.173C>T	p.Thr58Met	missense	Exon 1 of 5	NP_001074002.1	A6NIH7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UNC119B	ENST00000344651.5	TSL:2 MANE Select	c.173C>T	p.Thr58Met	missense	Exon 1 of 5	ENSP00000344942.4	A6NIH7
UNC119B	ENST00000718082.1		c.173C>T	p.Thr58Met	missense	Exon 1 of 4	ENSP00000520660.1	A0ABB0MV57
UNC119B	ENST00000953441.1		c.173C>T	p.Thr58Met	missense	Exon 1 of 3	ENSP00000623500.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1296448

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

639168

show subpopulations

African (AFR)

AF:

0.0000381

AC:

AN:

26234

American (AMR)

AF:

0.00

AC:

AN:

23294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22582

East Asian (EAS)

AF:

0.00

AC:

AN:

27604

South Asian (SAS)

AF:

0.00

AC:

AN:

70294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3802

European-Non Finnish (NFE)

AF:

0.0000125

AC:

AN:

1037038

Other (OTH)

AF:

0.0000187

AC:

AN:

53418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2088

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Benign

0.13

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.2

PhyloP100

3.6

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.048

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.011

Polyphen

0.82

Vest4

0.27

MutPred

0.38

Gain of helix (P = 0.0117)

MVP

0.043

MPC

0.97

ClinPred

0.98

GERP RS

1.4

PromoterAI

0.11

Neutral

(source)

Varity_R

0.18

gMVP

0.59

Mutation Taster

=83/17

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

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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