dbSNP rs773142214: USP17L4:p.Ser41* (chr8-7337236-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001256874.1(USP17L4):c.122C>A(p.Ser41*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000042 ( 0 hom., cov: 7)

Exomes 𝑓: 0.000081 ( 3 hom. )

Consequence

USP17L4
NM_001256874.1 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0720

Publications

0 publications found

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: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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 8-7337236-C-A is Benign according to our data. Variant chr8-7337236-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2658359.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256874.1. 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
	USP17L4	NM_001256874.1	MANE Select	c.122C>A	p.Ser41*	stop_gained	Exon 1 of 1	NP_001243803.1	A6NCW7
	FAM66B	NR_027423.2		n.617+11847G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP17L4	ENST00000526929.1	TSL:6 MANE Select	c.122C>A	p.Ser41*	stop_gained	Exon 1 of 1	ENSP00000485243.1	A6NCW7
FAM66B	ENST00000606573.1	TSL:1	n.703+11737G>T		intron	N/A
FAM66B	ENST00000529456.2	TSL:2	n.609+11847G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000417

AC:

AN:

47922

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:

0.0000723

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000151

AC:

AN:

72756

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000375

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000813

AC:

AN:

467258

Hom.:

Cov.:

AF XY:

0.0000644

AC XY:

AN XY:

248420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9974

American (AMR)

AF:

0.000238

AC:

AN:

25222

Ashkenazi Jewish (ASJ)

AF:

0.0000662

AC:

AN:

15102

East Asian (EAS)

AF:

0.00

AC:

AN:

30790

South Asian (SAS)

AF:

0.00

AC:

AN:

49070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30026

Middle Eastern (MID)

AF:

0.000498

AC:

AN:

2008

European-Non Finnish (NFE)

AF:

0.0000862

AC:

AN:

278562

Other (OTH)

AF:

0.000226

AC:

AN:

26504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000418

AC:

AN:

47902

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

21342

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

6456

American (AMR)

AF:

0.00

AC:

AN:

4404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1482

East Asian (EAS)

AF:

0.00

AC:

AN:

1974

South Asian (SAS)

AF:

0.00

AC:

AN:

1508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

164

European-Non Finnish (NFE)

AF:

0.0000724

AC:

AN:

27642

Other (OTH)

AF:

0.00

AC:

AN:

624

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000449

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

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.94

CADD

Uncertain

(source)

DANN

Benign

0.66

FATHMM_MKL

Benign

0.0089

PhyloP100

-0.072

Vest4

0.024

GERP RS

-0.50

PromoterAI

0.0092

Neutral

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over