chr3-49110192-C-T

Variant names:

• chr3-49110192-C-T
• rs2042932794
• NM_001199161.2:c.4030G>A

Variant summary

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

The NM_001199161.2(USP19):​c.4030G>A​(p.Ala1344Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP19 NM_001199161.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.74
• Publications: 0 publications found

Genes affected

USP19 (HGNC:12617): (ubiquitin specific peptidase 19) Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This protein is a ubiquitin protein ligase and plays a role in muscle wasting. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

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=0.12083581).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199161.2. 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
	USP19	NM_001199161.2	MANE Select	c.4030G>A	p.Ala1344Thr	missense	Exon 26 of 27	NP_001186090.1	O94966-6
	USP19	NM_001389594.1		c.4030G>A	p.Ala1344Thr	missense	Exon 26 of 27	NP_001376523.1	A0A8I5KXK1
	USP19	NM_001389595.1		c.4030G>A	p.Ala1344Thr	missense	Exon 26 of 27	NP_001376524.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP19	ENST00000417901.6	TSL:1 MANE Select	c.4030G>A	p.Ala1344Thr	missense	Exon 26 of 27	ENSP00000395260.1	O94966-6
	USP19	ENST00000398888.6	TSL:1	c.3721G>A	p.Ala1241Thr	missense	Exon 25 of 26	ENSP00000381863.2	O94966-1
	USP19	ENST00000398896.6	TSL:1	c.3682G>A	p.Ala1228Thr	missense	Exon 25 of 26	ENSP00000381870.3	O94966-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1365934 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 669266

African (AFR) AF: 0.00 AC: 0 AN: 30334

American (AMR) AF: 0.00 AC: 0 AN: 29080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20410

East Asian (EAS) AF: 0.00 AC: 0 AN: 38396

South Asian (SAS) AF: 0.00 AC: 0 AN: 70792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5318

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065746

Other (OTH) AF: 0.00 AC: 0 AN: 56040

GnomAD4 genome Cov.: 32

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	0.077
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.099
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N
PhyloP100		2.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.13
Sift	Benign	0.16	T
Sift4G	Benign	0.11	T
Polyphen		0.0030	B
Vest4		0.20
MutPred		0.35		Loss of helix (P = 0.0041)
MVP		0.13
MPC		0.53
ClinPred		0.34	T
GERP RS		4.6
Varity_R		0.12
gMVP		0.52
Mutation Taster		=65/35	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: rs2042932794; hg19: chr3-49147625;