2-61292273-T-G

Position:

• chr2-61292273-T-G

Variant summary

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

The NM_014709.4(USP34):​c.4548+1191A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,948 control chromosomes in the GnomAD database, including 10,183 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 (10183 hom., cov: 32)
• Consequence: USP34 NM_014709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445

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]

USP34 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP34	NM_014709.4	c.4548+1191A>C		intron_variant		ENST00000398571.7	NP_055524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP34	ENST00000398571.7	c.4548+1191A>C		intron_variant		5	NM_014709.4	ENSP00000381577.2
USP34	ENST00000472706.5	n.208+4527A>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55629 AN: 151830 Hom.: 10178 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.366 AC: 55655 AN: 151948 Hom.: 10183 Cov.: 32 AF XY: 0.361 AC XY: 26855 AN XY: 74304

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.339

Alfa AF: 0.357 Hom.: 10384

Bravo AF: 0.366

Asia WGS AF: 0.357 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.68

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: rs2167566; hg19: chr2-61519408;