Variant 8-7333694-C-G 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.1308C>G(p.His436Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,586,600 control chromosomes in the GnomAD database, including 373 homozygotes. 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 0.0037 ( 35 hom., cov: 24)

Exomes 𝑓: 0.0043 ( 338 hom. )

Consequence

USP17L1
NM_001256873.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.187

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=0.0054614246).

BP6

Variant 8-7333694-C-G is Benign according to our data. Variant chr8-7333694-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2658358.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP17L1	NM_001256873.1 linkuse as main transcript	c.1308C>G	p.His436Gln	missense_variant	1/1	ENST00000529559.1	NP_001243802.1	Q7RTZ2
FAM66B	NR_027423.2 linkuse as main transcript	n.618-8496G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP17L1	ENST00000529559.1 linkuse as main transcript	c.1308C>G	p.His436Gln	missense_variant	1/1	6	NM_001256873.1	ENSP00000485364.1		Q7RTZ2

Frequencies

GnomAD3 genomes

AF:

0.00370

AC:

515

AN:

139212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0342

Gnomad AMR

AF:

0.00490

Gnomad ASJ

AF:

0.0108

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00396

Gnomad FIN

AF:

0.00209

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00416

Gnomad OTH

AF:

0.00659

GnomAD3 exomes

AF:

0.00382

AC:

913

AN:

238928

Hom.:

AF XY:

0.00403

AC XY:

529

AN XY:

131308

show subpopulations

Gnomad AFR exome

AF:

0.000887

Gnomad AMR exome

AF:

0.00427

Gnomad ASJ exome

AF:

0.00750

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00456

Gnomad FIN exome

AF:

0.00195

Gnomad NFE exome

AF:

0.00430

Gnomad OTH exome

AF:

0.00626

GnomAD4 exome

AF:

0.00430

AC:

6226

AN:

1447312

Hom.:

338

Cov.:

AF XY:

0.00433

AC XY:

3120

AN XY:

720522

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00471

Gnomad4 ASJ exome

AF:

0.00877

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00468

Gnomad4 FIN exome

AF:

0.00170

Gnomad4 NFE exome

AF:

0.00447

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.00368

AC:

513

AN:

139288

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

240

AN XY:

68066

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.0108

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00396

Gnomad4 FIN

AF:

0.00209

Gnomad4 NFE

AF:

0.00413

Gnomad4 OTH

AF:

0.00651

Alfa

AF:

0.00227

Hom.:

ExAC

AF:

0.00365

AC:

421

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

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.1

DANN

Benign

0.63

DEOGEN2

Benign

0.0024

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0055

MutationAssessor

Benign

-0.95

PrimateAI

Uncertain

0.64

Sift4G

Benign

0.86

Vest4

0.091

MVP

0.067

GERP RS

-0.94

Varity_R

0.14

gMVP

0.027

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