rs13022976

Variant names:

• chr2-218520803-A-T
• rs13022976
• NM_020935.3:c.863+9153T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020935.3(USP37):​c.863+9153T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 152,286 control chromosomes in the GnomAD database, including 363 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 0.057 (363 hom., cov: 31)
• Consequence: USP37 NM_020935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 1 publications found

Genes affected

USP37 (HGNC:20063): (ubiquitin specific peptidase 37) Enables cysteine-type endopeptidase activity; protein kinase binding activity; and thiol-dependent deubiquitinase. Involved in G1/S transition of mitotic cell cycle; protein deubiquitination; and regulation of DNA replication. Located in nucleus. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP37	NM_020935.3	c.863+9153T>A		intron_variant	Intron 10 of 25	ENST00000258399.8	NP_065986.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP37	ENST00000258399.8	c.863+9153T>A		intron_variant	Intron 10 of 25	1	NM_020935.3	ENSP00000258399.3

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8626 AN: 152168 Hom.: 362 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0567 AC: 8640 AN: 152286 Hom.: 363 Cov.: 31 AF XY: 0.0554 AC XY: 4126 AN XY: 74468

African (AFR) AF: 0.110 AC: 4585 AN: 41552

American (AMR) AF: 0.0278 AC: 425 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3466

East Asian (EAS) AF: 0.117 AC: 608 AN: 5188

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4826

European-Finnish (FIN) AF: 0.0271 AC: 288 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0335 AC: 2278 AN: 68024

Other (OTH) AF: 0.0469 AC: 99 AN: 2112

Alfa AF: 0.0465 Hom.: 23

Bravo AF: 0.0599

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.48
PhyloP100		0.24
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: rs13022976; hg19: chr2-219385526;