dbSNP rs1259865765: USP35:p.Pro159Ser (chr11-78196720-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020798.4(USP35):c.475C>T(p.Pro159Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,378,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P159T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

USP35
NM_020798.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.258

Publications

0 publications found

Variant links:

Genes affected

USP35 (HGNC:20061): (ubiquitin specific peptidase 35) This gene encodes a member of the peptidase C19 family of ubiquitin-specific proteases. These deubiquitinating enzymes (DUBs) catalyze the removal of ubiquitin proteins from other proteins. The encoded protein associates with polarized mitochondria and has been shown to inhibit NF-kappa B activation and delay PARK2-mediated degradation of mitochondria. Expression of this gene is upregulated by the let-7a microRNA and reduced expression has been observed in human tumor tissues. [provided by RefSeq, Jul 2017]

USP35 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060661554).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020798.4. 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
	USP35	NM_020798.4	MANE Select	c.475C>T	p.Pro159Ser	missense	Exon 2 of 11	NP_065849.1	Q9P2H5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP35	ENST00000529308.6	TSL:5 MANE Select	c.475C>T	p.Pro159Ser	missense	Exon 2 of 11	ENSP00000431876.1	Q9P2H5-1
USP35	ENST00000528910.5	TSL:1	c.-59-1216C>T		intron	N/A	ENSP00000436001.1	E9PRM2
USP35	ENST00000869542.1		c.475C>T	p.Pro159Ser	missense	Exon 2 of 11	ENSP00000539601.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

126008

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1378252

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31140

American (AMR)

AF:

0.00

AC:

AN:

35536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25038

East Asian (EAS)

AF:

0.0000562

AC:

AN:

35566

South Asian (SAS)

AF:

0.00

AC:

AN:

78650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4226

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076952

Other (OTH)

AF:

0.00

AC:

AN:

57562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.75

M_CAP

Benign

0.030

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PhyloP100

0.26

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.56

REVEL

Benign

0.030

Sift

Benign

0.20

Sift4G

Uncertain

0.036

Polyphen

0.049

Vest4

0.16

MutPred

0.16

Gain of MoRF binding (P = 0.0552)

MVP

0.23

MPC

1.0

ClinPred

0.057

GERP RS

1.1

Varity_R

0.032

gMVP

0.17

Mutation Taster

=100/0

polymorphism

(source)

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

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