rs1332576115

Variant names:

• chr13-27171609-C-A
• rs1332576115
• NM_182488.4:c.31G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-27171609-C-A
• chr13-27171609-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182488.4(USP12):​c.31G>T​(p.Ala11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000233 in 1,289,738 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: USP12 NM_182488.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37
• 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]

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

ACMG classification

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=0.14044857).

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>T	p.Ala11Ser	missense	Exon 1 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.31G>T	p.Ala11Ser	missense	Exon 1 of 9	ENSP00000282344.6	O75317
	USP12	ENST00000963737.1		c.31G>T	p.Ala11Ser	missense	Exon 1 of 9	ENSP00000633796.1
	USP12	ENST00000915651.1		c.31G>T	p.Ala11Ser	missense	Exon 1 of 8	ENSP00000585710.1

Frequencies

GnomAD3 genomes AF: 0.00000683 AC: 1 AN: 146490 Hom.: 0 Cov.: 30

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: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1143248 Hom.: 0 Cov.: 31 AF XY: 0.00000176 AC XY: 1 AN XY: 567300

African (AFR) AF: 0.00 AC: 0 AN: 22044

American (AMR) AF: 0.00 AC: 0 AN: 28138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15188

East Asian (EAS) AF: 0.00 AC: 0 AN: 12102

South Asian (SAS) AF: 0.00 AC: 0 AN: 72142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2604

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 919988

Other (OTH) AF: 0.00 AC: 0 AN: 40138

GnomAD4 genome AF: 0.00000683 AC: 1 AN: 146490 Hom.: 0 Cov.: 30 AF XY: 0.0000140 AC XY: 1 AN XY: 71262

African (AFR) AF: 0.00 AC: 0 AN: 40828

American (AMR) AF: 0.00 AC: 0 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 5060

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65826

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		3.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.010	N
REVEL	Benign	0.068
Sift	Benign	0.28	T
Sift4G	Benign	0.83	T
Polyphen		0.0	B
Vest4		0.26
MutPred		0.34		Gain of disorder (P = 0.0505)
MVP		0.24
MPC		0.90
ClinPred		0.30	T
GERP RS		3.5
PromoterAI		-0.088	Neutral
Varity_R		0.14
gMVP		0.71
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs1332576115; hg19: chr13-27745746;