chr12-95533170-C-T

Variant names:

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

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]

USP44 links:

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
USP44	NM_032147.5 link	c.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	UniProt
USP44	ENST00000258499.8 link	c.1087G>A	p.Gly363Ser	missense_variant	Exon 2 of 6	1	NM_032147.5	ENSP00000258499.3	Q9H0E7
USP44	ENST00000393091.6 link	c.1087G>A	p.Gly363Ser	missense_variant	Exon 2 of 6	1		ENSP00000376806.2	Q9H0E7
USP44	ENST00000537435.2 link	c.1087G>A	p.Gly363Ser	missense_variant	Exon 2 of 6	1		ENSP00000442629.2	Q9H0E7
USP44	ENST00000552440.5 link	c.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.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00772

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00227

AC:

276

Asia WGS

AF:

0.00115

AC:

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

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

LIST_S2

Benign

0.35

.;.;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.2

N;N;.;N

PrimateAI

Benign

0.33

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over