Variant rs12539800 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_003344.4(UBE2H):c.336A>G(p.Leu112=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0798 in 1,613,644 control chromosomes in the GnomAD database, including 5,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.064 ( 371 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5346 hom. )

Consequence

UBE2H
NM_003344.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.74

Variant links:

Genes affected

UBE2H (HGNC:12484): (ubiquitin conjugating enzyme E2 H) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein sequence is 100% identical to the mouse homolog and 98% identical to the frog and zebrafish homologs. Three alternatively spliced transcript variants have been found for this gene and they encode distinct isoforms. [provided by RefSeq, Feb 2011]

UBE2H links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 7-129839298-T-C is Benign according to our data. Variant chr7-129839298-T-C is described in ClinVar as [Benign]. Clinvar id is 3056240.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBE2H	NM_003344.4 linkuse as main transcript	c.336A>G	p.Leu112=	synonymous_variant	6/7	ENST00000355621.8	NP_003335.1
UBE2H	NM_182697.3 linkuse as main transcript	c.243A>G	p.Leu81=	synonymous_variant	4/5		NP_874356.1
UBE2H	NM_001202498.2 linkuse as main transcript	c.126A>G	p.Leu42=	synonymous_variant	6/7		NP_001189427.1
UBE2H	XM_047420796.1 linkuse as main transcript	c.126A>G	p.Leu42=	synonymous_variant	7/8		XP_047276752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2H	ENST00000355621.8 linkuse as main transcript	c.336A>G	p.Leu112=	synonymous_variant	6/7	1	NM_003344.4	ENSP00000347836	P1	P62256-1

Frequencies

GnomAD3 genomes

AF:

0.0636

AC:

9665

AN:

151914

Hom.:

371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0539

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.0444

Gnomad SAS

AF:

0.0266

Gnomad FIN

AF:

0.0925

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0914

Gnomad OTH

AF:

0.0636

GnomAD3 exomes

AF:

0.0652

AC:

16382

AN:

251304

Hom.:

690

AF XY:

0.0656

AC XY:

8910

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.0398

Gnomad ASJ exome

AF:

0.0248

Gnomad EAS exome

AF:

0.0468

Gnomad SAS exome

AF:

0.0285

Gnomad FIN exome

AF:

0.0893

Gnomad NFE exome

AF:

0.0908

Gnomad OTH exome

AF:

0.0691

GnomAD4 exome

AF:

0.0814

AC:

119023

AN:

1461612

Hom.:

5346

Cov.:

AF XY:

0.0797

AC XY:

57920

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.0191

Gnomad4 AMR exome

AF:

0.0421

Gnomad4 ASJ exome

AF:

0.0251

Gnomad4 EAS exome

AF:

0.0298

Gnomad4 SAS exome

AF:

0.0284

Gnomad4 FIN exome

AF:

0.0839

Gnomad4 NFE exome

AF:

0.0929

Gnomad4 OTH exome

AF:

0.0688

GnomAD4 genome

AF:

0.0636

AC:

9669

AN:

152032

Hom.:

371

Cov.:

AF XY:

0.0629

AC XY:

4670

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0234

Gnomad4 AMR

AF:

0.0538

Gnomad4 ASJ

AF:

0.0277

Gnomad4 EAS

AF:

0.0447

Gnomad4 SAS

AF:

0.0264

Gnomad4 FIN

AF:

0.0925

Gnomad4 NFE

AF:

0.0915

Gnomad4 OTH

AF:

0.0616

Alfa

AF:

0.0763

Hom.:

252

Bravo

AF:

0.0593

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

UBE2H-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.79

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