rs17736515

chr2-85638995-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006590.4(USP39):c.1096-208T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 152,174 control chromosomes in the GnomAD database, including 218 homozygotes. 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: 𝑓 0.049 (218 hom., cov: 31)
• Consequence: USP39 NM_006590.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

Genes affected

USP39 (HGNC:20071): (ubiquitin specific peptidase 39) Predicted to enable thiol-dependent deubiquitinase and zinc ion binding activity. Involved in spliceosomal complex assembly. Located in nucleoplasm. Part of U4/U6 x U5 tri-snRNP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP39	NM_006590.4	c.1096-208T>A		intron_variant		ENST00000323701.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP39	ENST00000323701.11	c.1096-208T>A		intron_variant		1	NM_006590.4	P1

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7433 AN: 152056 Hom.: 217 Cov.: 31

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0600

Gnomad OTH AF: 0.0708

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0489 AC: 7441 AN: 152174 Hom.: 218 Cov.: 31 AF XY: 0.0469 AC XY: 3488 AN XY: 74396

Gnomad4 AFR AF: 0.0473

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0198

Gnomad4 NFE AF: 0.0600

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0572 Hom.: 28

Bravo AF: 0.0498

Asia WGS AF: 0.00808 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.5
Dann	Benign	0.52

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: rs17736515; hg19: chr2-85866118;