chr4-143185715-C-T

Variant names:

• chr4-143185715-C-T
• rs1731199967
• NM_032557.6:c.265C>T

Variant summary

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

The NM_032557.6(USP38):​c.265C>T​(p.Leu89Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP38 NM_032557.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.85
• 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 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP38	NM_032557.6	MANE Select	c.265C>T	p.Leu89Phe	missense	Exon 1 of 10	NP_115946.2	Q8NB14-1
	USP38	NM_001410848.1		c.265C>T	p.Leu89Phe	missense	Exon 1 of 9	NP_001397777.1	A0A804HIT0
	USP38	NM_001290325.1		c.265C>T	p.Leu89Phe	missense	Exon 1 of 9	NP_001277254.1	Q8NB14-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP38	ENST00000307017.9	TSL:1 MANE Select	c.265C>T	p.Leu89Phe	missense	Exon 1 of 10	ENSP00000303434.4	Q8NB14-1
	USP38	ENST00000510377.5	TSL:1	c.265C>T	p.Leu89Phe	missense	Exon 1 of 9	ENSP00000427647.1	Q8NB14-2
	USP38	ENST00000958020.1		c.265C>T	p.Leu89Phe	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	Benign	0.27
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Benign	0.096	T
Sift4G	Uncertain	0.013	D
Polyphen		0.97	D
Vest4		0.59
MutPred		0.31		Loss of loop (P = 0.1242)
MVP		0.90
MPC		1.9
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.54
gMVP		0.47
Mutation Taster		=27/73	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

dbSNP: rs1731199967; hg19: chr4-144106868;