chr2-61391463-C-T

Position:

• chr2-61391463-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• 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/exons	MANE	UniProt
USP34	NM_014709.4	c.753+3390G>A		intron_variant		ENST00000398571.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP34	ENST00000398571.7	c.753+3390G>A		intron_variant		5	NM_014709.4	P1
USP34	ENST00000453133.1	c.*143+3390G>A		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.0768

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.0911

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.134

Alfa AF: 0.128 Hom.: 236

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs17008940; hg19: chr2-61618598;