Genetic Variant USP38:p.Lys3Glu (chr4-143185457-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032557.6(USP38):c.7A>G(p.Lys3Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,432,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

USP38
NM_032557.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.27

Variant links:

Genes affected

USP38 (HGNC:20067): (ubiquitin specific peptidase 38) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

USP38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36525708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP38	NM_032557.6 link	c.7A>G	p.Lys3Glu	missense_variant	Exon 1 of 10	ENST00000307017.9	NP_115946.2	Q8NB14-1
USP38	NM_001410848.1 link	c.7A>G	p.Lys3Glu	missense_variant	Exon 1 of 9		NP_001397777.1
USP38	NM_001290325.1 link	c.7A>G	p.Lys3Glu	missense_variant	Exon 1 of 9		NP_001277254.1	Q8NB14-2
USP38	NM_001290326.1 link	c.-1475A>G		5_prime_UTR_variant	Exon 1 of 11		NP_001277255.1	Q8NB14B3KSB9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP38	ENST00000307017.9 link	c.7A>G	p.Lys3Glu	missense_variant	Exon 1 of 10	1	NM_032557.6	ENSP00000303434.4		Q8NB14-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000436

AC:

AN:

229158

Hom.:

AF XY:

0.00000817

AC XY:

AN XY:

122356

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000305

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1432286

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708404

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000468

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7A>G (p.K3E) alteration is located in exon 1 (coding exon 1) of the USP38 gene. This alteration results from a A to G substitution at nucleotide position 7, causing the lysine (K) at amino acid position 3 to be replaced by a glutamic acid (E). 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

0.88

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.65

.;P

Vest4

0.55

MutPred

0.21

Loss of ubiquitination at K3 (P = 0.011);Loss of ubiquitination at K3 (P = 0.011);

MVP

0.32

MPC

1.9

ClinPred

0.90

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.86

gMVP

0.73

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