Genetic Variant USP12:p.Ala11Thr (chr13-27171609-C-T) – 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_182488.4(USP12):c.31G>A(p.Ala11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000875 in 1,143,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. A11S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

USP12
NM_182488.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37

Publications

0 publications found

Variant links:

Genes affected

USP12 (HGNC:20485): (ubiquitin specific peptidase 12) Enables cysteine-type endopeptidase activity and thiol-dependent deubiquitinase. Involved in protein deubiquitination. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

USP12 links:

USP12-AS1 (HGNC:39961): (USP12 antisense RNA 1)

USP12-AS1 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=0.12908939).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182488.4. 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
	USP12	NM_182488.4	MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 1 of 9	NP_872294.2	O75317

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP12	ENST00000282344.11	TSL:1 MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 1 of 9	ENSP00000282344.6	O75317
USP12	ENST00000963737.1		c.31G>A	p.Ala11Thr	missense	Exon 1 of 9	ENSP00000633796.1
USP12	ENST00000915651.1		c.31G>A	p.Ala11Thr	missense	Exon 1 of 8	ENSP00000585710.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.75e-7

AC:

AN:

1143248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

567300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22044

American (AMR)

AF:

0.00

AC:

AN:

28138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15188

East Asian (EAS)

AF:

0.00

AC:

AN:

12102

South Asian (SAS)

AF:

0.00

AC:

AN:

72142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2604

European-Non Finnish (NFE)

AF:

0.00000109

AC:

AN:

919988

Other (OTH)

AF:

0.00

AC:

AN:

40138

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

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

0.24

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

3.4

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.10

REVEL

Benign

0.061

Sift

Benign

0.20

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.13

MutPred

0.42

Loss of ubiquitination at K9 (P = 0.0675)

MVP

0.17

MPC

0.95

ClinPred

0.43

GERP RS

3.5

PromoterAI

-0.17

Neutral

(source)

Varity_R

0.13

gMVP

0.81

Mutation Taster

=72/28

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