Genetic Variant USP38:p.Ser420Gly (chr4-143206081-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is . The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032557.6(USP38):c.1258A>G(p.Ser420Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,972 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: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

USP38
NM_032557.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Publications

0 publications found

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:

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new If you want to explore the variant's impact on the transcript NM_032557.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032557.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP38	NM_032557.6	MANE Select	c.1258A>G	p.Ser420Gly	missense	Exon 6 of 10	NP_115946.2	Q8NB14-1
USP38	NM_001410848.1		c.1156A>G	p.Ser386Gly	missense	Exon 5 of 9	NP_001397777.1	A0A804HIT0
USP38	NM_001290325.1		c.1258A>G	p.Ser420Gly	missense	Exon 6 of 9	NP_001277254.1	Q8NB14-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP38	ENST00000307017.9	TSL:1 MANE Select	c.1258A>G	p.Ser420Gly	missense	Exon 6 of 10	ENSP00000303434.4	Q8NB14-1
USP38	ENST00000510377.5	TSL:1	c.1258A>G	p.Ser420Gly	missense	Exon 6 of 9	ENSP00000427647.1	Q8NB14-2
USP38	ENST00000958020.1		c.1258A>G	p.Ser420Gly	missense	Exon 6 of 10	ENSP00000628079.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1459972

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

85740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111314

Other (OTH)

AF:

0.00

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000548

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

M_CAP

Benign

0.030

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.55

MutationAssessor

Benign

0.48

PhyloP100

9.3

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.0

REVEL

Benign

0.17

Sift

Benign

0.051

Sift4G

Benign

0.30

Varity_R

0.24

gMVP

0.52

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over