NM_006590.4:c.1096-208T>A

Variant names:

• chr2-85638995-T-A
• rs17736515
• NM_006590.4:c.1096-208T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006590.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP39	NM_006590.4	MANE Select	c.1096-208T>A		intron	N/A	NP_006581.2
	USP39	NM_001256725.2		c.1096-208T>A		intron	N/A	NP_001243654.1
	USP39	NM_001256726.2		c.1096-208T>A		intron	N/A	NP_001243655.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP39	ENST00000323701.11	TSL:1 MANE Select	c.1096-208T>A		intron	N/A	ENSP00000312981.6
	USP39	ENST00000409470.5	TSL:1	c.1096-208T>A		intron	N/A	ENSP00000386864.1
	USP39	ENST00000409025.5	TSL:5	c.1096-208T>A		intron	N/A	ENSP00000386572.1

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

African (AFR) AF: 0.0473 AC: 1962 AN: 41518

American (AMR) AF: 0.0504 AC: 769 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4822

European-Finnish (FIN) AF: 0.0198 AC: 210 AN: 10610

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0600 AC: 4079 AN: 68000

Other (OTH) AF: 0.0701 AC: 148 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.52
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs17736515; hg19: chr2-85866118;