chr4-143185514-G-T

Variant names:

• chr4-143185514-G-T
• NM_032557.6:c.64G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001290326.1(USP38):​c.-1418G>T 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 benign 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: 6.63
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21759272).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290326.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP38	NM_032557.6	MANE Select	c.64G>T	p.Val22Leu	missense	Exon 1 of 10	NP_115946.2	Q8NB14-1
	USP38	NM_001290326.1		c.-1418G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001277255.1	B3KSB9
	USP38	NM_001410848.1		c.64G>T	p.Val22Leu	missense	Exon 1 of 9	NP_001397777.1	A0A804HIT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP38	ENST00000307017.9	TSL:1 MANE Select	c.64G>T	p.Val22Leu	missense	Exon 1 of 10	ENSP00000303434.4	Q8NB14-1
	USP38	ENST00000510377.5	TSL:1	c.64G>T	p.Val22Leu	missense	Exon 1 of 9	ENSP00000427647.1	Q8NB14-2
	USP38	ENST00000958020.1		c.64G>T	p.Val22Leu	missense	Exon 1 of 10	ENSP00000628079.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	0.037
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.055
Sift	Uncertain	0.027	D
Sift4G	Benign	0.064	T
Polyphen		0.025	B
Vest4		0.42
MutPred		0.28		Loss of methylation at K24 (P = 0.1034)
MVP		0.23
MPC		0.84
ClinPred		0.96	D
GERP RS		4.4
PromoterAI		0.018	Neutral
Varity_R		0.59
gMVP		0.51
Mutation Taster		=39/61	disease causing

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

Other links and lift over

hg19: chr4-144106667;