Variant 7-43948652-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015983.4(UBE2D4):c.219T>G(p.Ile73Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

UBE2D4
NM_015983.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.433

Variant links:

Genes affected

UBE2D4 (HGNC:21647): (ubiquitin conjugating enzyme E2 D4 (putative)) Enables ubiquitin conjugating enzyme activity. Involved in protein polyubiquitination. Acts upstream of or within protein ubiquitination. Predicted to be part of ubiquitin ligase complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

UBE2D4 links:

POLR2J4 (HGNC:):

POLR2J4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2D4	NM_015983.4 linkuse as main transcript	c.219T>G	p.Ile73Met	missense_variant	5/7	ENST00000222402.8
POLR2J4	NR_003655.3 linkuse as main transcript	n.2267-2328A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2D4	ENST00000222402.8 linkuse as main transcript	c.219T>G	p.Ile73Met	missense_variant	5/7	1	NM_015983.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250272

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457096

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

Feb 07, 2023

The c.219T>G (p.I73M) alteration is located in exon 5 (coding exon 5) of the UBE2D4 gene. This alteration results from a T to G substitution at nucleotide position 219, causing the isoleucine (I) at amino acid position 73 to be replaced by a methionine (M). 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.0092

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.071

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.0053

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.057

T;T

Polyphen

0.93

P;.

Vest4

0.73

MutPred

0.82

Loss of catalytic residue at I73 (P = 0.01);Loss of catalytic residue at I73 (P = 0.01);

MVP

0.58

MPC

1.1

ClinPred

0.92

GERP RS

0.066

Varity_R

0.58

gMVP

0.61

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