Genetic Variant USP17L7:p.Phe49Val (chr8-12133865-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_001256869.2(USP17L7):c.145T>G(p.Phe49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,377,324 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 35)

Exomes 𝑓: 0.00015 ( 26 hom. )

Failed GnomAD Quality Control

Consequence

USP17L7
NM_001256869.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

USP17L7 (HGNC:37180): (ubiquitin specific peptidase 17 like family member 7) 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]

USP17L7 links:

FAM66D (HGNC:24159): (family with sequence similarity 66 member D)

FAM66D 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=0.0062601864).

BP6

Variant 8-12133865-A-C is Benign according to our data. Variant chr8-12133865-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658420.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP17L7	NM_001256869.2 link	c.145T>G	p.Phe49Val	missense_variant	Exon 1 of 1	ENST00000530447.5	NP_001243798.1	P0C7H9
FAM66D	NR_027425.1 link	n.609-11558A>C		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP17L7	ENST00000530447.5 link	c.145T>G	p.Phe49Val	missense_variant	Exon 1 of 1	6	NM_001256869.2	ENSP00000485337.2		P0C7H9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

204

AN:

143668

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000777

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000681

Gnomad SAS

AF:

0.000248

Gnomad FIN

AF:

0.0000994

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000458

Gnomad OTH

AF:

0.00206

GnomAD3 exomes

AF:

0.000462

AC:

107

AN:

231408

Hom.:

AF XY:

0.000348

AC XY:

AN XY:

126574

show subpopulations

Gnomad AFR exome

AF:

0.00509

Gnomad AMR exome

AF:

0.0000906

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.000449

Gnomad SAS exome

AF:

0.000440

Gnomad FIN exome

AF:

0.000144

Gnomad NFE exome

AF:

0.0000473

Gnomad OTH exome

AF:

0.00122

GnomAD4 exome

AF:

0.000152

AC:

209

AN:

1377324

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

685490

show subpopulations

Gnomad4 AFR exome

AF:

0.00348

Gnomad4 AMR exome

AF:

0.000232

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.000350

Gnomad4 SAS exome

AF:

0.000364

Gnomad4 FIN exome

AF:

0.000138

Gnomad4 NFE exome

AF:

0.0000246

Gnomad4 OTH exome

AF:

0.000247

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00141

AC:

203

AN:

143776

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

69874

show subpopulations

Gnomad4 AFR

AF:

0.00460

Gnomad4 AMR

AF:

0.000776

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000683

Gnomad4 SAS

AF:

0.000248

Gnomad4 FIN

AF:

0.0000994

Gnomad4 NFE

AF:

0.0000458

Gnomad4 OTH

AF:

0.00204

Alfa

AF:

0.000488

Hom.:

ExAC

AF:

0.00110

AC:

123

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

USP17L7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.39

CADD

Benign

2.1

DANN

Benign

0.19

DEOGEN2

Benign

0.0023

FATHMM_MKL

Benign

0.000090

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0063

MutationAssessor

Benign

-0.69

Sift4G

Benign

0.73

Vest4

0.023

MVP

0.17

Varity_R

0.069

gMVP

0.040

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