rs2042932794

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-49110192-C-A
• chr3-49110192-C-T

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>T​(p.Ala1344Ser) 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. 15/22 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. A1344T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP19 NM_001199161.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.16210476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP19	NM_001199161.2	c.4030G>T	p.Ala1344Ser	missense_variant	Exon 26 of 27	ENST00000417901.6	NP_001186090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP19	ENST00000417901.6	c.4030G>T	p.Ala1344Ser	missense_variant	Exon 26 of 27	1	NM_001199161.2	ENSP00000395260.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.0067	.;.;.;T;T;.
Eigen	Benign	0.096
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	.;T;T;.;D;D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;.;.;.;L;.
PhyloP100		2.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.010	N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.098	T;T;T;D;D;D
Sift4G	Benign	0.24	T;T;T;D;D;D
Polyphen		0.29, 0.19	.;.;.;B;B;.
Vest4		0.30
MutPred		0.31		Loss of helix (P = 0.0017);.;.;Loss of helix (P = 0.0017);.;.;
MVP		0.15
MPC		0.51
ClinPred		0.44	T
GERP RS		4.6
Varity_R		0.13
gMVP		0.42
Mutation Taster		=81/19	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;