Variant 4-52628116-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000441222.8(USP46):c.165C>T(p.Phe55=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00209 in 1,613,950 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0095 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 23 hom. )

Consequence

USP46
ENST00000441222.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.43

Variant links:

Genes affected

USP46 (HGNC:20075): (ubiquitin specific peptidase 46) Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP46 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Jun 2009]

USP46 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 4-52628116-G-A is Benign according to our data. Variant chr4-52628116-G-A is described in ClinVar as [Benign]. Clinvar id is 769633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00952 (1450/152300) while in subpopulation AFR AF= 0.0327 (1359/41536). AF 95% confidence interval is 0.0313. There are 19 homozygotes in gnomad4. There are 693 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP46	NM_022832.4 linkuse as main transcript	c.165C>T	p.Phe55=	synonymous_variant	3/9	ENST00000441222.8	NP_073743.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP46	ENST00000441222.8 linkuse as main transcript	c.165C>T	p.Phe55=	synonymous_variant	3/9	1	NM_022832.4	ENSP00000407818	P1	P62068-1

Frequencies

GnomAD3 genomes

AF:

0.00951

AC:

1448

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00267

AC:

664

AN:

248974

Hom.:

AF XY:

0.00202

AC XY:

273

AN XY:

135056

show subpopulations

Gnomad AFR exome

AF:

0.0344

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.000796

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000496

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00132

AC:

1929

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

802

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0340

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000497

Gnomad4 OTH exome

AF:

0.00205

GnomAD4 genome

AF:

0.00952

AC:

1450

AN:

152300

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

693

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0327

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00553

Hom.:

Bravo

AF:

0.0107

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.85

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