4-143203520-A-G

Variant names:

• chr4-143203520-A-G
• NM_032557.6:c.1163A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001290326.1(USP38):​c.-319A>G variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP38 NM_001290326.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP38	NM_032557.6	c.1163A>G	p.Tyr388Cys	missense_variant	Exon 5 of 10	ENST00000307017.9	NP_115946.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP38	ENST00000307017.9	c.1163A>G	p.Tyr388Cys	missense_variant	Exon 5 of 10	1	NM_032557.6	ENSP00000303434.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1163A>G (p.Y388C) alteration is located in exon 5 (coding exon 5) of the USP38 gene. This alteration results from a A to G substitution at nucleotide position 1163, causing the tyrosine (Y) at amino acid position 388 to be replaced by a cysteine (C). 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	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.98	.;D
Vest4		0.90
MutPred		0.47		Loss of glycosylation at S389 (P = 0.0331);Loss of glycosylation at S389 (P = 0.0331);
MVP		0.87
MPC		0.57
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.64
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-144124673;