chr4-143185878-T-C

Variant names:

• chr4-143185878-T-C
• NM_032557.6:c.428T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032557.6(USP38):​c.428T>C​(p.Leu143Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: USP38 NM_032557.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP38	NM_032557.6	c.428T>C	p.Leu143Pro	missense_variant	Exon 1 of 10	ENST00000307017.9	NP_115946.2
USP38	NM_001410848.1	c.428T>C	p.Leu143Pro	missense_variant	Exon 1 of 9		NP_001397777.1
USP38	NM_001290325.1	c.428T>C	p.Leu143Pro	missense_variant	Exon 1 of 9		NP_001277254.1
USP38	NM_001290326.1	c.-1054T>C		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.428T>C	p.Leu143Pro	missense_variant	Exon 1 of 10	1	NM_032557.6	ENSP00000303434.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	.;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.040	D;D
Sift4G	Benign	0.070	T;T
Polyphen		0.95	.;P
Vest4		0.74
MutPred		0.39		Gain of disorder (P = 0.0133);Gain of disorder (P = 0.0133);
MVP		0.86
MPC		2.1
ClinPred		0.89	D
GERP RS		4.9
Varity_R		0.88
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-144107031;