12-95533170-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032147.5(USP44):​c.1087G>A​(p.Gly363Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,614,146 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00069 ( 17 hom. )

Consequence

USP44
NM_032147.5 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.11
Variant links:
Genes affected
USP44 (HGNC:20064): (ubiquitin specific peptidase 44) The protein encoded by this gene is a protease that functions as a deubiquitinating enzyme. The encoded protein is thought to help regulate the spindle assembly checkpoint by preventing early anaphase onset. This protein specifically deubiquitinates CDC20, which stabilizes the anaphase promoting complex/cyclosome. [provided by RefSeq, Dec 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0016607344).
BP6
Variant 12-95533170-C-T is Benign according to our data. Variant chr12-95533170-C-T is described in ClinVar as [Benign]. Clinvar id is 715654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00694 (1056/152258) while in subpopulation AFR AF= 0.0241 (1001/41544). AF 95% confidence interval is 0.0229. There are 8 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP44NM_032147.5 linkc.1087G>A p.Gly363Ser missense_variant Exon 2 of 6 ENST00000258499.8 NP_115523.2 Q9H0E7A0A024RBD7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USP44ENST00000258499.8 linkc.1087G>A p.Gly363Ser missense_variant Exon 2 of 6 1 NM_032147.5 ENSP00000258499.3 Q9H0E7
USP44ENST00000393091.6 linkc.1087G>A p.Gly363Ser missense_variant Exon 2 of 6 1 ENSP00000376806.2 Q9H0E7
USP44ENST00000537435.2 linkc.1087G>A p.Gly363Ser missense_variant Exon 2 of 6 1 ENSP00000442629.2 Q9H0E7
USP44ENST00000552440.5 linkc.1087G>A p.Gly363Ser missense_variant Exon 1 of 3 5 ENSP00000448670.1 F8VRI7

Frequencies

GnomAD3 genomes
AF:
0.00693
AC:
1054
AN:
152140
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00288
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00174
AC:
438
AN:
251408
Hom.:
7
AF XY:
0.00132
AC XY:
180
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.0234
Gnomad AMR exome
AF:
0.00124
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.000694
AC:
1014
AN:
1461888
Hom.:
17
Cov.:
30
AF XY:
0.000582
AC XY:
423
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0244
Gnomad4 AMR exome
AF:
0.00132
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.00189
GnomAD4 genome
AF:
0.00694
AC:
1056
AN:
152258
Hom.:
8
Cov.:
32
AF XY:
0.00637
AC XY:
474
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0241
Gnomad4 AMR
AF:
0.00288
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.000919
Hom.:
2
Bravo
AF:
0.00772
ESP6500AA
AF:
0.0204
AC:
90
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00227
AC:
276
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 26, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

USP44-related disorder Benign:1
Sep 06, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.71
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
4.1
DANN
Benign
0.54
DEOGEN2
Benign
0.0034
T;T;.;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.35
.;.;T;T
MetaRNN
Benign
0.0017
T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-1.2
N;N;.;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.79
N;N;N;N
REVEL
Benign
0.032
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0
B;B;.;B
Vest4
0.025
MVP
0.12
MPC
0.16
ClinPred
0.00094
T
GERP RS
1.5
Varity_R
0.045
gMVP
0.22

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: rs61733460; hg19: chr12-95926946; API