4-143185540-G-T

Variant names:

• chr4-143185540-G-T
• NM_032557.6:c.90G>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.90G>T​(p.Glu30Asp) 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 1,461,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: USP38 NM_032557.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95

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=0.1596865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP38	NM_032557.6	c.90G>T	p.Glu30Asp	missense_variant	Exon 1 of 10	ENST00000307017.9	NP_115946.2
USP38	NM_001410848.1	c.90G>T	p.Glu30Asp	missense_variant	Exon 1 of 9		NP_001397777.1
USP38	NM_001290325.1	c.90G>T	p.Glu30Asp	missense_variant	Exon 1 of 9		NP_001277254.1
USP38	NM_001290326.1	c.-1392G>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.90G>T	p.Glu30Asp	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: 1461618 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727076

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.56
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.90	N;N
REVEL	Benign	0.11
Sift	Benign	0.13	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.97	.;D
Vest4		0.27
MutPred		0.17		Loss of MoRF binding (P = 0.2157);Loss of MoRF binding (P = 0.2157);
MVP		0.74
MPC		1.6
ClinPred		0.93	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.61
gMVP		0.30

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: chr4-144106693;