rs138466543

Variant names:

• chr2-218455710-T-A
• rs138466543
• NM_020935.3:c.2722A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-218455710-T-A
• chr2-218455710-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020935.3(USP37):​c.2722A>T​(p.Ile908Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP37 NM_020935.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.64

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP37	NM_020935.3	c.2722A>T	p.Ile908Phe	missense_variant	Exon 25 of 26	ENST00000258399.8	NP_065986.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP37	ENST00000258399.8	c.2722A>T	p.Ile908Phe	missense_variant	Exon 25 of 26	1	NM_020935.3	ENSP00000258399.3
USP37	ENST00000418019.5	c.2722A>T	p.Ile908Phe	missense_variant	Exon 25 of 26	1		ENSP00000396585.1
USP37	ENST00000415516.5	c.2440A>T	p.Ile814Phe	missense_variant	Exon 23 of 24	1		ENSP00000400902.1
USP37	ENST00000454775.5	c.2722A>T	p.Ile908Phe	missense_variant	Exon 25 of 26	2		ENSP00000393662.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 247148 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133552

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T;T;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	.;.;D;D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-0.72	T
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.98	D;D;D;D
Vest4		0.87
MVP		0.38
MPC		1.3
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs138466543; hg19: chr2-219320433;