Variant chr8-7338417-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001256874.1(USP17L4):c.1303G>A(p.Asp435Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 12)

Exomes 𝑓: 0.00077 ( 26 hom. )

Failed GnomAD Quality Control

Consequence

USP17L4
NM_001256874.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49

Variant links:

Genes affected

USP17L4 (HGNC:37176): (ubiquitin specific peptidase 17 like family member 4) 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]

USP17L4 links:

FAM66B (HGNC:):

FAM66B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014757335).

BP6

Variant 8-7338417-G-A is Benign according to our data. Variant chr8-7338417-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658360.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP17L4	NM_001256874.1 linkuse as main transcript	c.1303G>A	p.Asp435Asn	missense_variant	1/1	ENST00000526929.1	NP_001243803.1	A6NCW7
FAM66B	NR_027423.2 linkuse as main transcript	n.617+10666C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP17L4	ENST00000526929.1 linkuse as main transcript	c.1303G>A	p.Asp435Asn	missense_variant	1/1	6	NM_001256874.1	ENSP00000485243.1		A6NCW7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

98080

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000995

Gnomad ASJ

AF:

0.000709

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00285

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000211

Gnomad OTH

AF:

0.00161

GnomAD3 exomes

AF:

0.000854

AC:

AN:

52664

Hom.:

AF XY:

0.00112

AC XY:

AN XY:

26724

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00418

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000432

Gnomad OTH exome

AF:

0.00211

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000767

AC:

425

AN:

554150

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

301

AN XY:

294268

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000290

Gnomad4 ASJ exome

AF:

0.000728

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00455

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000359

Gnomad4 OTH exome

AF:

0.000651

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000255

AC:

AN:

98102

Hom.:

Cov.:

AF XY:

0.000347

AC XY:

AN XY:

46144

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000993

Gnomad4 ASJ

AF:

0.000709

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00285

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000211

Gnomad4 OTH

AF:

0.00159

Alfa

AF:

0.000320

Hom.:

ExAC

AF:

0.000130

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

Feb 01, 2023

USP17L4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.021

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.77

MetaRNN

Benign

0.015

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.68

Sift4G

Benign

0.40

Vest4

0.11

MVP

0.099

GERP RS

0.49

Varity_R

0.089

gMVP

0.0095

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