chr12-95533093-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032147.5(USP44):​c.1164G>T​(p.Leu388Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

USP44
NM_032147.5 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0310
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 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 rank MANE Protein UniProt
USP44NM_032147.5 linkc.1164G>T p.Leu388Phe 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.1164G>T p.Leu388Phe missense_variant Exon 2 of 6 1 NM_032147.5 ENSP00000258499.3 Q9H0E7
USP44ENST00000393091.6 linkc.1164G>T p.Leu388Phe missense_variant Exon 2 of 6 1 ENSP00000376806.2 Q9H0E7
USP44ENST00000537435.2 linkc.1164G>T p.Leu388Phe missense_variant Exon 2 of 6 1 ENSP00000442629.2 Q9H0E7
USP44ENST00000552440.5 linkc.1164G>T p.Leu388Phe missense_variant Exon 1 of 3 5 ENSP00000448670.1 F8VRI7

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251470
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135910
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000773
AC:
113
AN:
1461892
Hom.:
0
Cov.:
30
AF XY:
0.0000743
AC XY:
54
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000102
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000378
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1164G>T (p.L388F) alteration is located in exon 2 (coding exon 1) of the USP44 gene. This alteration results from a G to T substitution at nucleotide position 1164, causing the leucine (L) at amino acid position 388 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.87
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.080
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;T;.;T
Eigen
Uncertain
0.34
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.94
.;.;D;D
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.55
D;D;D;D
MetaSVM
Benign
-0.80
T
MutationAssessor
Pathogenic
3.2
M;M;.;M
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-3.6
D;D;D;D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0030
D;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
1.0
D;D;.;D
Vest4
0.87
MutPred
0.78
Loss of stability (P = 0.1272);Loss of stability (P = 0.1272);Loss of stability (P = 0.1272);Loss of stability (P = 0.1272);
MVP
0.70
MPC
0.70
ClinPred
0.95
D
GERP RS
1.0
Varity_R
0.65
gMVP
0.61

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: rs777867882; hg19: chr12-95926869; COSMIC: COSV51563413; COSMIC: COSV51563413; API