Genetic Variant USP17L7:p.Asp11Glu (chr8-12133977-G-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.33C>G(p.Asp11Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,147,188 control chromosomes in the GnomAD database, including 39 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 0.00018 ( 2 hom., cov: 35)

Exomes 𝑓: 0.00040 ( 37 hom. )

Consequence

USP17L7
NM_001256869.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.12

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=0.010778487).

BP6

Variant 8-12133977-G-C is Benign according to our data. Variant chr8-12133977-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658422.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP17L7	NM_001256869.2 link	c.33C>G	p.Asp11Glu	missense_variant	Exon 1 of 1	ENST00000530447.5	NP_001243798.1	P0C7H9
FAM66D	NR_027425.1 link	n.609-11446G>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.33C>G	p.Asp11Glu	missense_variant	Exon 1 of 1	6	NM_001256869.2	ENSP00000485337.2		P0C7H9

Frequencies

GnomAD3 genomes

AF:

0.000187

AC:

AN:

144452

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000756

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000211

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000489

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0208

Gnomad NFE

AF:

0.000183

Gnomad OTH

AF:

0.000512

GnomAD3 exomes

AF:

0.000461

AC:

105

AN:

227992

Hom.:

AF XY:

0.000617

AC XY:

AN XY:

124852

show subpopulations

Gnomad AFR exome

AF:

0.0000731

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000258

Gnomad SAS exome

AF:

0.00205

Gnomad FIN exome

AF:

0.0000552

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000397

AC:

398

AN:

1002626

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

261

AN XY:

514522

show subpopulations

Gnomad4 AFR exome

AF:

0.000116

Gnomad4 AMR exome

AF:

0.0000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00257

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.000253

Gnomad4 OTH exome

AF:

0.000409

GnomAD4 genome

AF:

0.000180

AC:

AN:

144562

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

70236

show subpopulations

Gnomad4 AFR

AF:

0.0000753

Gnomad4 AMR

AF:

0.000211

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000490

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000183

Gnomad4 OTH

AF:

0.000507

Alfa

AF:

0.000158

Hom.:

ExAC

AF:

0.000402

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM66D: BS2; USP17L7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

1.3

DANN

Benign

0.34

DEOGEN2

Benign

0.0021

FATHMM_MKL

Benign

0.00019

LIST_S2

Benign

0.34

MetaRNN

Benign

0.011

MutationAssessor

Benign

-0.63

Sift4G

Benign

1.0

Vest4

0.041

MVP

0.081

Varity_R

0.14

gMVP

0.028

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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