Variant 12-109067525-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_032663.5(USP30):c.378C>A(p.Ala126=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,612,980 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 49 hom. )

Consequence

USP30
NM_032663.5 splice_region, synonymous

Scores

Splicing: ADA: 0.0001175

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.843

Variant links:

Genes affected

USP30 (HGNC:20065): (ubiquitin specific peptidase 30) USP30, a member of the ubiquitin-specific protease family (see USP1, MIM 603478), is a novel mitochondrial deubiquitinating (DUB) enzyme (Nakamura and Hirose, 2008 [PubMed 18287522]).[supplied by OMIM, Dec 2008]

USP30 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 12-109067525-C-A is Benign according to our data. Variant chr12-109067525-C-A is described in ClinVar as [Benign]. Clinvar id is 770233.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.843 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00206 (3008/1460906) while in subpopulation AMR AF= 0.0194 (865/44522). AF 95% confidence interval is 0.0184. There are 49 homozygotes in gnomad4_exome. There are 1372 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP30	NM_032663.5 linkuse as main transcript	c.378C>A	p.Ala126=	splice_region_variant, synonymous_variant	4/13	ENST00000257548.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP30	ENST00000257548.10 linkuse as main transcript	c.378C>A	p.Ala126=	splice_region_variant, synonymous_variant	4/13	1	NM_032663.5	P2

Frequencies

GnomAD3 genomes

AF:

0.00353

AC:

537

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00597

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0350

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000971

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00626

AC:

1571

AN:

250880

Hom.:

AF XY:

0.00533

AC XY:

723

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0207

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.0342

Gnomad NFE exome

AF:

0.000678

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00206

AC:

3008

AN:

1460906

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1372

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0194

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.0344

Gnomad4 NFE exome

AF:

0.000151

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.00354

AC:

538

AN:

152074

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

364

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00603

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0350

Gnomad4 NFE

AF:

0.000971

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000600

Hom.:

Bravo

AF:

0.00165

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.016

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