Variant 8-7333183-C-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.797C>T(p.Thr266Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 17)

Exomes 𝑓: 0.00021 ( 7 hom. )

Consequence

USP17L1
NM_001256873.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.967

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=0.054819375).

BP6

Variant 8-7333183-C-T is Benign according to our data. Variant chr8-7333183-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658355.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP17L1	NM_001256873.1 linkuse as main transcript	c.797C>T	p.Thr266Met	missense_variant	1/1	ENST00000529559.1	NP_001243802.1	Q7RTZ2
FAM66B	NR_027423.2 linkuse as main transcript	n.618-7985G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP17L1	ENST00000529559.1 linkuse as main transcript	c.797C>T	p.Thr266Met	missense_variant	1/1	6	NM_001256873.1	ENSP00000485364.1		Q7RTZ2

Frequencies

GnomAD3 genomes

AF:

0.000137

AC:

AN:

117026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000253

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

142710

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

78016

show subpopulations

Gnomad AFR exome

AF:

0.000215

Gnomad AMR exome

AF:

0.000244

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000915

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000172

Gnomad OTH exome

AF:

0.000703

GnomAD4 exome

AF:

0.000212

AC:

147

AN:

692726

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

AN XY:

365446

show subpopulations

Gnomad4 AFR exome

AF:

0.0000790

Gnomad4 AMR exome

AF:

0.000169

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:

0.000294

Gnomad4 OTH exome

AF:

0.000263

GnomAD4 genome

AF:

0.000137

AC:

AN:

117026

Hom.:

Cov.:

AF XY:

0.0000529

AC XY:

AN XY:

56760

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000253

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000289

Hom.:

ExAC

AF:

0.0000789

AC:

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

Dec 01, 2022

FAM66B: BS2; USP17L1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.016

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.33

MetaRNN

Benign

0.055

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.62

Sift4G

Benign

0.086

Vest4

0.12

MVP

0.15

GERP RS

-0.45

Varity_R

0.049

gMVP

0.084

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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