rs10496092

Variant names:

• chr2-61297544-C-T
• rs10496092
• NM_014709.4:c.4129-619G>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.4129-619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,032 control chromosomes in the GnomAD database, including 8,536 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 0.33 (8536 hom., cov: 32)
• Consequence: USP34 NM_014709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 10 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]

USP34 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP34	NM_014709.4	MANE Select	c.4129-619G>A		intron	N/A	NP_055524.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP34	ENST00000398571.7	TSL:5 MANE Select	c.4129-619G>A		intron	N/A	ENSP00000381577.2	Q70CQ2-1
	USP34	ENST00000472706.5	TSL:4	n.83-619G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50568 AN: 151914 Hom.: 8533 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.333 AC: 50593 AN: 152032 Hom.: 8536 Cov.: 32 AF XY: 0.329 AC XY: 24486 AN XY: 74314

African (AFR) AF: 0.266 AC: 11020 AN: 41472

American (AMR) AF: 0.327 AC: 4983 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1711 AN: 5172

South Asian (SAS) AF: 0.373 AC: 1802 AN: 4826

European-Finnish (FIN) AF: 0.324 AC: 3423 AN: 10562

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25540 AN: 67958

Other (OTH) AF: 0.314 AC: 662 AN: 2110

Alfa AF: 0.329 Hom.: 3517

Bravo AF: 0.327

Asia WGS AF: 0.352 AC: 1220 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.46
PhyloP100		-0.83
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: rs10496092; hg19: chr2-61524679;