chr13-27116593-C-T

Variant names:

• chr13-27116593-C-T
• rs771072514
• NM_182488.4:c.52G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_182488.4(USP12):​c.52G>A​(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,610,742 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 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: USP12 NM_182488.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16826585).
• BS2: High AC in GnomAd4 at 5 AD gene.

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.52G>A	p.Ala18Thr	missense	Exon 2 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.52G>A	p.Ala18Thr	missense	Exon 2 of 9	ENSP00000282344.6	O75317
	USP12	ENST00000963737.1		c.52G>A	p.Ala18Thr	missense	Exon 2 of 9	ENSP00000633796.1
	USP12	ENST00000915651.1		c.49-10649G>A		intron	N/A	ENSP00000585710.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152138 Hom.: 0 Cov.: 31

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250070 AF XY: 0.0000222

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: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1458604 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 725528

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4480

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111402

Other (OTH) AF: 0.0000332 AC: 2 AN: 60184

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152138 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000966 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000329

EpiControl AF: 0.00

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	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.021
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.26	N
PhyloP100		3.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.043
Sift	Benign	0.38	T
Sift4G	Benign	0.35	T
Polyphen		0.0060	B
Vest4		0.37
MVP		0.28
MPC		0.95
ClinPred		0.34	T
GERP RS		4.4
Varity_R		0.13
gMVP		0.76
Mutation Taster		=36/64	disease causing

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: rs771072514; hg19: chr13-27690730;