Variant chr1-21715390-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_032236.8(USP48):c.1962T>C(p.His654=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,589,658 control chromosomes in the GnomAD database, including 21 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 0.0046 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 16 hom. )

Consequence

USP48
NM_032236.8 splice_region, synonymous

Scores

Splicing: ADA: 0.03784

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

USP48 (HGNC:18533): (ubiquitin specific peptidase 48) This gene encodes a protein containing domains that associate it with the peptidase family C19, also known as family 2 of ubiquitin carboxyl-terminal hydrolases. Family members function as deubiquitinating enzymes, recognizing and hydrolyzing the peptide bond at the C-terminal glycine of ubiquitin. Enzymes in peptidase family C19 are involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

USP48 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 1-21715390-A-G is Benign according to our data. Variant chr1-21715390-A-G is described in ClinVar as [Benign]. Clinvar id is 2672327.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.6 with no splicing effect.

BS2

High AC in GnomAd4 at 700 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP48	NM_032236.8 linkuse as main transcript	c.1962T>C	p.His654=	splice_region_variant, synonymous_variant	15/27	ENST00000308271.14	NP_115612.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP48	ENST00000308271.14 linkuse as main transcript	c.1962T>C	p.His654=	splice_region_variant, synonymous_variant	15/27	1	NM_032236.8	ENSP00000309262	P1	Q86UV5-1

Frequencies

GnomAD3 genomes

AF:

0.00459

AC:

699

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00214

AC:

529

AN:

247582

Hom.:

AF XY:

0.00192

AC XY:

257

AN XY:

133926

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000670

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000275

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.000941

AC:

1352

AN:

1437296

Hom.:

Cov.:

AF XY:

0.000921

AC XY:

660

AN XY:

716252

show subpopulations

Gnomad4 AFR exome

AF:

0.0155

Gnomad4 AMR exome

AF:

0.00180

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000823

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00459

AC:

700

AN:

152362

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.00535

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.000656

EpiControl

AF:

0.000297

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

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

USP48: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.038

dbscSNV1_RF

Benign

0.14

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