Variant 8-7333291-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001256873.1(USP17L1):c.905A>T(p.Asp302Val) variant causes a missense change. The variant allele was found at a frequency of 0.00117 in 1,185,168 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 8 hom., cov: 21)

Exomes 𝑓: 0.0011 ( 39 hom. )

Consequence

USP17L1
NM_001256873.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.82

Variant links:

Genes affected

USP17L1 (HGNC:37182): (ubiquitin specific peptidase 17 like family member 1) 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]

USP17L1 links:

FAM66B (HGNC:):

FAM66B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009993553).

BP6

Variant 8-7333291-A-T is Benign according to our data. Variant chr8-7333291-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658356.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP17L1	NM_001256873.1 linkuse as main transcript	c.905A>T	p.Asp302Val	missense_variant	1/1	ENST00000529559.1	NP_001243802.1	Q7RTZ2
FAM66B	NR_027423.2 linkuse as main transcript	n.618-8093T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP17L1	ENST00000529559.1 linkuse as main transcript	c.905A>T	p.Asp302Val	missense_variant	1/1	6	NM_001256873.1	ENSP00000485364.1		Q7RTZ2

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

192

AN:

125088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000732

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00890

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00145

Gnomad OTH

AF:

0.000565

GnomAD3 exomes

AF:

0.00169

AC:

335

AN:

198098

Hom.:

AF XY:

0.00155

AC XY:

168

AN XY:

108712

show subpopulations

Gnomad AFR exome

AF:

0.000479

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00173

GnomAD4 exome

AF:

0.00112

AC:

1191

AN:

1060034

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

613

AN XY:

544228

show subpopulations

Gnomad4 AFR exome

AF:

0.000254

Gnomad4 AMR exome

AF:

0.000139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00839

Gnomad4 NFE exome

AF:

0.000949

Gnomad4 OTH exome

AF:

0.000455

GnomAD4 genome

AF:

0.00153

AC:

192

AN:

125134

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

112

AN XY:

60906

show subpopulations

Gnomad4 AFR

AF:

0.000281

Gnomad4 AMR

AF:

0.0000731

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00890

Gnomad4 NFE

AF:

0.00145

Gnomad4 OTH

AF:

0.000559

Alfa

AF:

0.00144

Hom.:

ExAC

AF:

0.00123

AC:

140

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

FAM66B: BS2; USP17L1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Benign

0.64

DEOGEN2

Benign

0.058

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.010

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.67

Sift4G

Pathogenic

0.0

Vest4

0.47

MVP

0.42

GERP RS

0.60

Varity_R

0.16

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over