2-61292273-T-G

Variant names:

• chr2-61292273-T-G
• rs2167566
• NM_014709.4:c.4548+1191A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014709.4. 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
	USP34	NM_014709.4	MANE Select	c.4548+1191A>C		intron	N/A	NP_055524.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP34	ENST00000398571.7	TSL:5 MANE Select	c.4548+1191A>C		intron	N/A	ENSP00000381577.2
	USP34	ENST00000472706.5	TSL:4	n.208+4527A>C		intron	N/A

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

African (AFR) AF: 0.383 AC: 15878 AN: 41460

American (AMR) AF: 0.338 AC: 5159 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3472

East Asian (EAS) AF: 0.335 AC: 1732 AN: 5176

South Asian (SAS) AF: 0.375 AC: 1804 AN: 4814

European-Finnish (FIN) AF: 0.323 AC: 3403 AN: 10530

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25568 AN: 67904

Other (OTH) AF: 0.339 AC: 716 AN: 2114

Alfa AF: 0.362 Hom.: 15300

Bravo AF: 0.366

Asia WGS AF: 0.357 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.45
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: rs2167566; hg19: chr2-61519408;