Genetic Variant USP17L8:p.Pro25Pro (chr8-7973179-T-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_001256872.1(USP17L8):c.75A>G(p.Pro25Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P25P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00016 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

USP17L8
NM_001256872.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.524

Publications

2 publications found

Variant links:

Genes affected

USP17L8 (HGNC:37181): (ubiquitin specific peptidase 17 like family member 8) 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]

USP17L8 links:

LOC124901865 (HGNC:):

LOC124901865 links:

FAM66E (HGNC:18735): (family with sequence similarity 66 member E)

FAM66E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-0.524 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256872.1. 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
	USP17L8	NM_001256872.1	MANE Select	c.75A>G	p.Pro25Pro	synonymous	Exon 1 of 1	NP_001243801.1	P0C7I0
	FAM66E	NR_027424.1		n.610+11883T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP17L8	ENST00000527080.1	TSL:6 MANE Select	c.75A>G	p.Pro25Pro	synonymous	Exon 1 of 1	ENSP00000485306.1	P0C7I0
FAM66E	ENST00000529252.2	TSL:2	n.609+11883T>C		intron	N/A
FAM66E	ENST00000533615.1	TSL:2	n.1154-11086T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

23616

Hom.:

Cov.:

Gnomad AFR

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000301

AC:

AN:

23218

AF XY:

0.000527

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000628

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000159

AC:

AN:

81772

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

AN XY:

42920

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20454

American (AMR)

AF:

0.00

AC:

AN:

5124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

916

East Asian (EAS)

AF:

0.000419

AC:

AN:

4774

South Asian (SAS)

AF:

0.000171

AC:

AN:

11692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

380

European-Non Finnish (NFE)

AF:

0.000293

AC:

AN:

30732

Other (OTH)

AF:

0.00

AC:

AN:

5738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.611

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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

23704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11110

African (AFR)

AF:

0.00

AC:

AN:

21572

American (AMR)

AF:

0.00

AC:

AN:

870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

168

South Asian (SAS)

AF:

0.00

AC:

AN:

154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

680

Other (OTH)

AF:

0.00

AC:

AN:

224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

7.1

(source)

DANN

Benign

0.31

PhyloP100

-0.52

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over