Genetic Variant USP17L1:p.Thr266Met (chr8-7333183-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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:28890): (family with sequence similarity 66 member B)

FAM66B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2658355.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256873.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L1	NM_001256873.1	MANE Select	c.797C>T	p.Thr266Met	missense	Exon 1 of 1	NP_001243802.1	Q7RTZ2
	FAM66B	NR_027423.2		n.618-7985G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP17L1	ENST00000529559.1	TSL:6 MANE Select	c.797C>T	p.Thr266Met	missense	Exon 1 of 1	ENSP00000485364.1	Q7RTZ2
FAM66B	ENST00000606573.1	TSL:1	n.704-7768G>A		intron	N/A
FAM66B	ENST00000529456.2	TSL:2	n.610-7985G>A		intron	N/A

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

GnomAD2 exomes

AF:

0.000147

AC:

AN:

142710

AF XY:

0.000141

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 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

African (AFR)

AF:

0.0000790

AC:

AN:

12654

American (AMR)

AF:

0.000169

AC:

AN:

35410

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20726

East Asian (EAS)

AF:

0.00

AC:

AN:

33356

South Asian (SAS)

AF:

0.00

AC:

AN:

67078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2642

European-Non Finnish (NFE)

AF:

0.000294

AC:

131

AN:

446150

Other (OTH)

AF:

0.000263

AC:

AN:

34274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000137

AC:

AN:

117026

Hom.:

Cov.:

AF XY:

0.0000529

AC XY:

AN XY:

56760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17362

American (AMR)

AF:

0.00

AC:

AN:

12802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3204

East Asian (EAS)

AF:

0.00

AC:

AN:

4346

South Asian (SAS)

AF:

0.00

AC:

AN:

3612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000253

AC:

AN:

63246

Other (OTH)

AF:

0.00

AC:

AN:

1560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000289

Hom.:

ExAC

AF:

0.0000789

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

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

PhyloP100

0.97

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over