chr3-49109135-C-T

Variant names:

• chr3-49109135-C-T
• rs374391542
• ENST00000398888.6:c.3780G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001389594.1(USP19):​c.4089G>A​(p.Glu1363Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000771 in 1,529,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: USP19 NM_001389594.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.547
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-49109135-C-T is Benign according to our data. Variant chr3-49109135-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 737304.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.547 with no splicing effect.
• BS2: High AC in GnomAd4 at 70 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389594.1. 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.4039-607G>A		intron	N/A	NP_001186090.1	O94966-6
	USP19	NM_001389594.1		c.4089G>A	p.Glu1363Glu	synonymous	Exon 27 of 27	NP_001376523.1	A0A8I5KXK1
	USP19	NM_001389595.1		c.4089G>A	p.Glu1363Glu	synonymous	Exon 27 of 27	NP_001376524.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP19	ENST00000398888.6	TSL:1	c.3780G>A	p.Glu1260Glu	synonymous	Exon 26 of 26	ENSP00000381863.2	O94966-1
	USP19	ENST00000417901.6	TSL:1 MANE Select	c.4039-607G>A		intron	N/A	ENSP00000395260.1	O94966-6
	USP19	ENST00000398896.6	TSL:1	c.3691-607G>A		intron	N/A	ENSP00000381870.3	O94966-4

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000141 AC: 19 AN: 134512 AF XY: 0.000137

Gnomad AFR exome AF: 0.00231

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000349 AC: 48 AN: 1377330 Hom.: 0 Cov.: 30 AF XY: 0.0000353 AC XY: 24 AN XY: 679412

African (AFR) AF: 0.00133 AC: 40 AN: 30042

American (AMR) AF: 0.000144 AC: 4 AN: 27874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23180

East Asian (EAS) AF: 0.00 AC: 0 AN: 36258

South Asian (SAS) AF: 0.00 AC: 0 AN: 76592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48384

Middle Eastern (MID) AF: 0.000181 AC: 1 AN: 5516

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072780

Other (OTH) AF: 0.0000529 AC: 3 AN: 56704

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.000444 AC XY: 33 AN XY: 74392

African (AFR) AF: 0.00152 AC: 63 AN: 41526

American (AMR) AF: 0.000392 AC: 6 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67972

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000355 Hom.: 0

Bravo AF: 0.000638

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.77
PhyloP100		0.55

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: rs374391542; hg19: chr3-49146568;