NM_032557.6:c.367C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1717858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP38	NM_032557.6	c.367C>T	p.Leu123Phe	missense_variant	Exon 1 of 10	ENST00000307017.9	NP_115946.2
USP38	NM_001410848.1	c.367C>T	p.Leu123Phe	missense_variant	Exon 1 of 9		NP_001397777.1
USP38	NM_001290325.1	c.367C>T	p.Leu123Phe	missense_variant	Exon 1 of 9		NP_001277254.1
USP38	NM_001290326.1	c.-1115C>T		5_prime_UTR_variant	Exon 1 of 11		NP_001277255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP38	ENST00000307017.9	c.367C>T	p.Leu123Phe	missense_variant	Exon 1 of 10	1	NM_032557.6	ENSP00000303434.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.056
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.91	.;P
Vest4		0.34
MutPred		0.28		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP		0.82
MPC		1.7
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.38
gMVP		0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs770626867; hg19: chr4-144106970;