rs17008940

Variant names:

• chr2-61391463-C-T
• rs17008940
• NM_014709.4:c.753+3390G>A

Variant summary

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

The NM_014709.4(USP34):​c.753+3390G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,080 control chromosomes in the GnomAD database, including 1,491 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 0.13 (1491 hom., cov: 32)
• Consequence: USP34 NM_014709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP34	NM_014709.4	c.753+3390G>A		intron_variant	Intron 5 of 79	ENST00000398571.7	NP_055524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP34	ENST00000398571.7	c.753+3390G>A		intron_variant	Intron 5 of 79	5	NM_014709.4	ENSP00000381577.2
USP34	ENST00000453133.1	n.*143+3390G>A		intron_variant	Intron 3 of 12	5		ENSP00000388129.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19528 AN: 151962 Hom.: 1489 Cov.: 32

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.128 AC: 19537 AN: 152080 Hom.: 1491 Cov.: 32 AF XY: 0.132 AC XY: 9824 AN XY: 74348

African (AFR) AF: 0.0768 AC: 3184 AN: 41466

American (AMR) AF: 0.171 AC: 2605 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1516 AN: 5172

South Asian (SAS) AF: 0.318 AC: 1534 AN: 4824

European-Finnish (FIN) AF: 0.0911 AC: 965 AN: 10588

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8686 AN: 67970

Other (OTH) AF: 0.134 AC: 283 AN: 2110

Alfa AF: 0.126 Hom.: 239

Bravo AF: 0.131

Asia WGS AF: 0.296 AC: 1030 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.71
PhyloP100		-0.010
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
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: rs17008940; hg19: chr2-61618598;