Genetic Variant USP17L19:p.Ser23Pro (chr4-9253444-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001256860.1(USP17L19):c.67T>C(p.Ser23Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Benign (★).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.18 ( 200 hom. )

Failed GnomAD Quality Control

Consequence

USP17L19
NM_001256860.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.533

Publications

1 publications found

Variant links:

Genes affected

USP17L19 (HGNC:44447): (ubiquitin specific peptidase 17 like family member 19) Predicted to enable cysteine-type endopeptidase activity and thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination and regulation of apoptotic process. Predicted to be located in endoplasmic reticulum. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

USP17L19 links:

ENSG00000288075 (HGNC:):

ENSG00000288075 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025346875).

BP6

Variant 4-9253444-T-C is Benign according to our data. Variant chr4-9253444-T-C is described in ClinVar as Benign. ClinVar VariationId is 1206218.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256860.1. 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
	USP17L19	NM_001256860.1	MANE Select	c.67T>C	p.Ser23Pro	missense	Exon 1 of 1	NP_001243789.1	D6RCP7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP17L19	ENST00000515566.1	TSL:6 MANE Select	c.67T>C	p.Ser23Pro	missense	Exon 1 of 1	ENSP00000425582.1	D6RCP7
ENSG00000288075	ENST00000658713.1		n.487-49955A>G		intron	N/A
ENSG00000288075	ENST00000666840.2		n.643+121643A>G		intron	N/A

Frequencies

GnomAD3 genomes

AC:

AN:

Hom.:

Cov.:

GnomAD2 exomes

AF:

0.179

AC:

196

AN:

1094

AF XY:

0.163

show subpopulations

Gnomad AFR exome

AF:

0.450

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0614

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.176

AC:

469

AN:

2664

Hom.:

200

Cov.:

AF XY:

0.123

AC XY:

204

AN XY:

1656

show subpopulations

African (AFR)

AF:

0.824

AC:

140

AN:

170

American (AMR)

AF:

0.316

AC:

AN:

228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0530

AC:

AN:

264

South Asian (SAS)

AF:

0.0346

AC:

AN:

1214

European-Finnish (FIN)

AF:

0.214

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.215

AC:

139

AN:

648

Other (OTH)

AF:

0.473

AC:

AN:

112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Alfa

AF:

0.644

Hom.:

2149

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0080

Eigen

Benign

-0.83

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.53

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.83

REVEL

Benign

0.034

Sift

Benign

0.30

Sift4G

Benign

0.22

Vest4

0.11

ClinPred

0.0052

GERP RS

0.37

PromoterAI

0.0068

Neutral

(source)

Varity_R

0.091

gMVP

0.037

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over