rs10034164

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022832.4(USP46):​c.*4075T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,270 control chromosomes in the GnomAD database, including 3,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3020 hom., cov: 33)
Exomes 𝑓: 0.13 ( 1 hom. )

Consequence

USP46
NM_022832.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02
Variant links:
Genes affected
USP46 (HGNC:20075): (ubiquitin specific peptidase 46) Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP46 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Jun 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
USP46NM_022832.4 linkuse as main transcriptc.*4075T>C 3_prime_UTR_variant 9/9 ENST00000441222.8 NP_073743.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
USP46ENST00000441222.8 linkuse as main transcriptc.*4075T>C 3_prime_UTR_variant 9/91 NM_022832.4 ENSP00000407818 P1P62068-1

Frequencies

GnomAD3 genomes
AF:
0.179
AC:
27244
AN:
152112
Hom.:
2995
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.323
Gnomad AMI
AF:
0.106
Gnomad AMR
AF:
0.140
Gnomad ASJ
AF:
0.138
Gnomad EAS
AF:
0.158
Gnomad SAS
AF:
0.126
Gnomad FIN
AF:
0.119
Gnomad MID
AF:
0.111
Gnomad NFE
AF:
0.118
Gnomad OTH
AF:
0.172
GnomAD4 exome
AF:
0.125
AC:
5
AN:
40
Hom.:
1
Cov.:
0
AF XY:
0.133
AC XY:
4
AN XY:
30
show subpopulations
Gnomad4 EAS exome
AF:
0.500
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0588
GnomAD4 genome
AF:
0.180
AC:
27327
AN:
152230
Hom.:
3020
Cov.:
33
AF XY:
0.178
AC XY:
13274
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.324
Gnomad4 AMR
AF:
0.140
Gnomad4 ASJ
AF:
0.138
Gnomad4 EAS
AF:
0.157
Gnomad4 SAS
AF:
0.126
Gnomad4 FIN
AF:
0.119
Gnomad4 NFE
AF:
0.118
Gnomad4 OTH
AF:
0.175
Alfa
AF:
0.156
Hom.:
395
Bravo
AF:
0.191
Asia WGS
AF:
0.170
AC:
592
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.35
DANN
Benign
0.45

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

LitVar

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

Other links and lift over

dbSNP: rs10034164; hg19: chr4-53459731; API