rs201834559

Variant names:

• chr3-49108968-C-A
• rs201834559
• ENST00000398888.6:c.3947G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-49108968-C-A
• chr3-49108968-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001389594.1(USP19):​c.4256G>T​(p.Arg1419Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R1419H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: USP19 NM_001389594.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.094420016).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP19	NM_001199161.2	c.4039-440G>T		intron_variant	Intron 26 of 26	ENST00000417901.6	NP_001186090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP19	ENST00000417901.6	c.4039-440G>T		intron_variant	Intron 26 of 26	1	NM_001199161.2	ENSP00000395260.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1457160 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724670

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000541

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.28	N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.070	T;T;T
Polyphen		0.039	B;B;.
Vest4		0.23
MutPred		0.28		Loss of MoRF binding (P = 0.0266);.;.;
MVP		0.21
MPC		0.82
ClinPred		0.28	T
GERP RS		1.0
Varity_R		0.080
gMVP		0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs201834559; hg19: chr3-49146401;