Variant chr1-154558457-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017582.7(UBE2Q1):c.97G>T(p.Gly33Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,387,388 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 2 hom. )

Consequence

UBE2Q1
NM_017582.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.693

Variant links:

Genes affected

UBE2Q1 (HGNC:15698): (ubiquitin conjugating enzyme E2 Q1) 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 (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein is 98% identical to the mouse counterpart. [provided by RefSeq, Jul 2008]

UBE2Q1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03472647).

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2Q1	NM_017582.7 linkuse as main transcript	c.97G>T	p.Gly33Trp	missense_variant	1/13	ENST00000292211.5	NP_060052.3
UBE2Q1	XM_047424467.1 linkuse as main transcript	c.97G>T	p.Gly33Trp	missense_variant	1/12		XP_047280423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2Q1	ENST00000292211.5 linkuse as main transcript	c.97G>T	p.Gly33Trp	missense_variant	1/13	1	NM_017582.7	ENSP00000292211	P1	Q7Z7E8-1
UBE2Q1	ENST00000497453.1 linkuse as main transcript	n.122-92G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000114

AC:

AN:

149592

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000594

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.0000597

Gnomad OTH

AF:

0.000486

GnomAD3 exomes

AF:

0.000460

AC:

AN:

45644

Hom.:

AF XY:

0.000533

AC XY:

AN XY:

28128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00146

Gnomad SAS exome

AF:

0.00129

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000165

Gnomad OTH exome

AF:

0.000822

GnomAD4 exome

AF:

0.000139

AC:

172

AN:

1237686

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

608302

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000346

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000183

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.0000303

Gnomad4 NFE exome

AF:

0.0000706

Gnomad4 OTH exome

AF:

0.000259

GnomAD4 genome

AF:

0.000114

AC:

AN:

149702

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73156

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000596

Gnomad4 SAS

AF:

0.00126

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000597

Gnomad4 OTH

AF:

0.000481

ExAC

AF:

0.000535

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.97G>T (p.G33W) alteration is located in exon 1 (coding exon 1) of the UBE2Q1 gene. This alteration results from a G to T substitution at nucleotide position 97, causing the glycine (G) at amino acid position 33 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.020

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.52

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.96

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.16

REVEL

Benign

0.056

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.84

Vest4

0.29

MutPred

0.20

Loss of relative solvent accessibility (P = 0.0186);

MVP

0.043

MPC

1.3

ClinPred

0.15

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.22

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