3-33400264-T-C

Variant names:

Variant summary

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

The NM_014517.5(UBP1):c.1105A>G(p.Thr369Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,601,344 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UBP1
NM_014517.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Publications

3 publications found

Variant links:

Genes affected

UBP1 (HGNC:12507): (upstream binding protein 1) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of viral transcription and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

UBP1 links:

FBXL2 (HGNC:13598): (F-box and leucine rich repeat protein 2) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains 12 tandem leucine-rich repeats. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

FBXL2 links:

Genome browser will be placed here

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=0.11306661).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014517.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBP1	NM_014517.5	MANE Select	c.1105A>G	p.Thr369Ala	missense	Exon 11 of 16	NP_055332.3
UBP1	NM_001128161.2		c.1105A>G	p.Thr369Ala	missense	Exon 12 of 17	NP_001121633.1	Q9NZI7-1
UBP1	NM_001128160.2		c.997A>G	p.Thr333Ala	missense	Exon 10 of 15	NP_001121632.1	Q9NZI7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBP1	ENST00000283629.8	TSL:1 MANE Select	c.1105A>G	p.Thr369Ala	missense	Exon 11 of 16	ENSP00000283629.3	Q9NZI7-1
UBP1	ENST00000283628.9	TSL:2	c.1105A>G	p.Thr369Ala	missense	Exon 12 of 17	ENSP00000283628.5	Q9NZI7-1
UBP1	ENST00000908179.1		c.1105A>G	p.Thr369Ala	missense	Exon 12 of 17	ENSP00000578238.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000840

AC:

AN:

238006

AF XY:

0.0000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1449136

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32546

American (AMR)

AF:

0.00

AC:

AN:

41048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.00

AC:

AN:

39244

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108476

Other (OTH)

AF:

0.0000167

AC:

AN:

59946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

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:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000113

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

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.010

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

2.7

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

REVEL

Benign

0.086

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0090

Polyphen

0.23

Vest4

0.23

MutPred

0.21

Gain of glycosylation at T369 (P = 0.0643)

MVP

0.17

MPC

0.26

ClinPred

0.47

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.54

Mutation Taster

=46/54

disease causing

(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