Genetic Variant USP34:p.Ala3462Ala (chr2-61188357-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014709.4(USP34):c.10386T>C(p.Ala3462Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,613,356 control chromosomes in the GnomAD database, including 177,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17238 hom., cov: 32)

Exomes 𝑓: 0.46 ( 160346 hom. )

Consequence

USP34
NM_014709.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.341

Variant links:

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 links:

AHSA2P (HGNC:20437): (activator of HSP90 ATPase homolog 2, pseudogene) Predicted to enable ATPase activator activity. Predicted to be involved in positive regulation of ATPase activity and protein folding. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

AHSA2P links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-61188357-A-G is Benign according to our data. Variant chr2-61188357-A-G is described in ClinVar as [Benign]. Clinvar id is 1229915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.341 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP34	NM_014709.4 link	c.10386T>C	p.Ala3462Ala	synonymous_variant	Exon 80 of 80	ENST00000398571.7	NP_055524.3	Q70CQ2-1
AHSA2P	NR_152210.1 link	n.2547A>G		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP34	ENST00000398571.7 link	c.10386T>C	p.Ala3462Ala	synonymous_variant	Exon 80 of 80	5	NM_014709.4	ENSP00000381577.2		Q70CQ2-1

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71644

AN:

151870

Hom.:

17213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.600

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.483

GnomAD3 exomes

AF:

0.441

AC:

110120

AN:

249468

Hom.:

25533

AF XY:

0.437

AC XY:

59173

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.491

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.497

Gnomad EAS exome

AF:

0.373

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.592

Gnomad NFE exome

AF:

0.486

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.463

AC:

676756

AN:

1461368

Hom.:

160346

Cov.:

AF XY:

0.458

AC XY:

333222

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.494

Gnomad4 AMR exome

AF:

0.355

Gnomad4 ASJ exome

AF:

0.503

Gnomad4 EAS exome

AF:

0.358

Gnomad4 SAS exome

AF:

0.270

Gnomad4 FIN exome

AF:

0.581

Gnomad4 NFE exome

AF:

0.478

Gnomad4 OTH exome

AF:

0.466

GnomAD4 genome

AF:

0.472

AC:

71716

AN:

151988

Hom.:

17238

Cov.:

AF XY:

0.474

AC XY:

35201

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.488

Gnomad4 AMR

AF:

0.402

Gnomad4 ASJ

AF:

0.507

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.600

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.481

Alfa

AF:

0.461

Hom.:

6795

Bravo

AF:

0.460

Asia WGS

AF:

0.318

AC:

1109

AN:

3478

EpiCase

AF:

0.482

EpiControl

AF:

0.487

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 01, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.3

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over