rs2593633

chr2-61344378-T-C

Variant summary

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

The NM_014709.4(USP34):c.2286-349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,050 control chromosomes in the GnomAD database, including 10,299 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 0.37 (10299 hom., cov: 32)
• Consequence: USP34 NM_014709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

Genes affected

USP34 (HGNC:20066): (ubiquitin specific peptidase 34) Enables cysteine-type endopeptidase activity and thiol-dependent deubiquitinase. Involved in positive regulation of canonical Wnt signaling pathway and protein K48-linked deubiquitination. Predicted to be active in cytosol and nucleus. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP34	NM_014709.4	c.2286-349A>G		intron_variant		ENST00000398571.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP34	ENST00000398571.7	c.2286-349A>G		intron_variant		5	NM_014709.4	P1
USP34	ENST00000460004.1	n.251-349A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55941 AN: 151930 Hom.: 10296 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.368 AC: 55969 AN: 152050 Hom.: 10299 Cov.: 32 AF XY: 0.363 AC XY: 26966 AN XY: 74342

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.336

Alfa AF: 0.378 Hom.: 2595

Bravo AF: 0.368

Asia WGS AF: 0.357 AC: 1238 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.9
Dann	Benign	0.75

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: rs2593633; hg19: chr2-61571513;