4-143185817-C-T

Variant names:

• chr4-143185817-C-T
• rs770626867
• NM_032557.6:c.367C>T

Variant summary

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

The NM_032557.6(USP38):​c.367C>T​(p.Leu123Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L123V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP38 NM_032557.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• 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=0.1717858).

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.367C>T	p.Leu123Phe	missense	Exon 1 of 10	NP_115946.2	Q8NB14-1
	USP38	NM_001410848.1		c.367C>T	p.Leu123Phe	missense	Exon 1 of 9	NP_001397777.1	A0A804HIT0
	USP38	NM_001290325.1		c.367C>T	p.Leu123Phe	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.367C>T	p.Leu123Phe	missense	Exon 1 of 10	ENSP00000303434.4	Q8NB14-1
	USP38	ENST00000510377.5	TSL:1	c.367C>T	p.Leu123Phe	missense	Exon 1 of 9	ENSP00000427647.1	Q8NB14-2
	USP38	ENST00000958020.1		c.367C>T	p.Leu123Phe	missense	Exon 1 of 10	ENSP00000628079.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.42
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.056
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.016	D
Polyphen		0.91	P
Vest4		0.34
MutPred		0.28		Loss of helix (P = 0.3949)
MVP		0.82
MPC		1.7
ClinPred		0.96	D
GERP RS		5.0
PromoterAI		0.016	Neutral
Varity_R		0.38
gMVP		0.42
Mutation Taster		=57/43	polymorphism

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: rs770626867; hg19: chr4-144106970;