Genetic Variant NM_203412.2:c.454C>T (chr1-110112988-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_203412.2(UBL4B):c.454C>T(p.Leu152Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,606,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBL4B
NM_203412.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.270

Publications

0 publications found

Variant links:

Genes affected

UBL4B (HGNC:32309): (ubiquitin like 4B) Involved in positive regulation of protein targeting to mitochondrion. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

UBL4B links:

LINC01397 (HGNC:50677): (long intergenic non-protein coding RNA 1397)

LINC01397 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048010767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203412.2. 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
	UBL4B	NM_203412.2	MANE Select	c.454C>T	p.Leu152Phe	missense	Exon 1 of 1	NP_981957.1	Q8N7F7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBL4B	ENST00000334179.5	TSL:6 MANE Select	c.454C>T	p.Leu152Phe	missense	Exon 1 of 1	ENSP00000334044.3	Q8N7F7
	LINC01397	ENST00000751945.1		n.464+3575C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

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:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000427

AC:

AN:

234084

AF XY:

0.00000782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000574

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1454742

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33310

American (AMR)

AF:

0.00

AC:

AN:

43590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25818

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39536

South Asian (SAS)

AF:

0.00

AC:

AN:

85166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1109182

Other (OTH)

AF:

0.00

AC:

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Benign

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.7

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.36

M_CAP

Benign

0.0066

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.27

PrimateAI

Benign

0.23

PROVEAN

Benign

0.26

REVEL

Benign

0.094

Sift

Benign

0.048

Sift4G

Benign

0.069

Polyphen

0.56

Vest4

0.036

MutPred

0.073

Loss of helix (P = 0.1706)

MVP

0.15

MPC

0.29

ClinPred

0.39

GERP RS

1.1

Varity_R

0.044

gMVP

0.026

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over