11-78200217-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020798.4(USP35):c.1021C>T(p.His341Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
USP35
NM_020798.4 missense
NM_020798.4 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 7.91
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USP35 | NM_020798.4 | c.1021C>T | p.His341Tyr | missense_variant | 5/11 | ENST00000529308.6 | NP_065849.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USP35 | ENST00000529308.6 | c.1021C>T | p.His341Tyr | missense_variant | 5/11 | 5 | NM_020798.4 | ENSP00000431876 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249502Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135372
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461866Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727240
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2023 | The c.1021C>T (p.H341Y) alteration is located in exon 5 (coding exon 4) of the USP35 gene. This alteration results from a C to T substitution at nucleotide position 1021, causing the histidine (H) at amino acid position 341 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;D;D
Polyphen
1.0
.;D;.
Vest4
0.63, 0.74
MutPred
0.55
.;Loss of disorder (P = 0.1693);.;
MVP
MPC
0.095
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at