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GeneBe

3-179708794-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_003940.3(USP13):c.642C>T(p.Cys214=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,614,068 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 88 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 89 hom. )

Consequence

USP13
NM_003940.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.88
Variant links:
Genes affected
USP13 (HGNC:12611): (ubiquitin specific peptidase 13) Enables several functions, including BAT3 complex binding activity; chaperone binding activity; and cysteine-type peptidase activity. Involved in several processes, including maintenance of unfolded protein involved in ERAD pathway; regulation of cellular catabolic process; and regulation of transcription, DNA-templated. Acts upstream of or within protein deubiquitination and protein stabilization. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-179708794-C-T is Benign according to our data. Variant chr3-179708794-C-T is described in ClinVar as [Benign]. Clinvar id is 708775.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.88 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
USP13NM_003940.3 linkuse as main transcriptc.642C>T p.Cys214= synonymous_variant 6/21 ENST00000263966.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
USP13ENST00000263966.8 linkuse as main transcriptc.642C>T p.Cys214= synonymous_variant 6/211 NM_003940.3 P4Q92995-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0179
AC:
2722
AN:
152108
Hom.:
86
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0631
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00426
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00484
AC:
1217
AN:
251408
Hom.:
42
AF XY:
0.00369
AC XY:
502
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.0659
Gnomad AMR exome
AF:
0.00254
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000352
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00187
AC:
2732
AN:
1461842
Hom.:
89
Cov.:
30
AF XY:
0.00160
AC XY:
1162
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0639
Gnomad4 AMR exome
AF:
0.00295
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000290
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.000150
Gnomad4 OTH exome
AF:
0.00412
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0180
AC:
2738
AN:
152226
Hom.:
88
Cov.:
32
AF XY:
0.0174
AC XY:
1297
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0632
Gnomad4 AMR
AF:
0.00425
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00524
Hom.:
26
Bravo
AF:
0.0201
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.000491
EpiControl
AF:
0.000415

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
9.5
Dann
Benign
0.55
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11917211; hg19: chr3-179426582; COSMIC: COSV99831913; API