13-27069377-T-C

Variant names:

• chr13-27069377-T-C
• NM_182488.4:c.1019A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182488.4(USP12):​c.1019A>G​(p.Asp340Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP12 NM_182488.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

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.1019A>G	p.Asp340Gly	missense	Exon 9 of 9	NP_872294.2	O75317

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP12	ENST00000282344.11	TSL:1 MANE Select	c.1019A>G	p.Asp340Gly	missense	Exon 9 of 9	ENSP00000282344.6	O75317
	USP12	ENST00000963737.1		c.983A>G	p.Asp328Gly	missense	Exon 9 of 9	ENSP00000633796.1
	USP12	ENST00000915651.1		c.938A>G	p.Asp313Gly	missense	Exon 8 of 8	ENSP00000585710.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.029	D
Polyphen		0.96	D
Vest4		0.74
MutPred		0.54		Gain of ubiquitination at K338 (P = 0.0716)
MVP		0.58
MPC		1.7
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.76
gMVP		0.63
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr13-27643514;