Variant 1-10106409-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001105562.3(UBE4B):c.1022C>T(p.Ser341Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

UBE4B
NM_001105562.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

UBE4B (HGNC:12500): (ubiquitination factor E4B) 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 an additional conjugation factor, E4, which is involved in multiubiquitin chain assembly. This gene is also the strongest candidate in the neuroblastoma tumor suppressor genes. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

UBE4B 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=0.010897309).

BS2

High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4B	NM_001105562.3 linkuse as main transcript	c.1022C>T	p.Ser341Phe	missense_variant	7/28	ENST00000343090.11	NP_001099032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE4B	ENST00000343090.11 linkuse as main transcript	c.1022C>T	p.Ser341Phe	missense_variant	7/28	1	NM_001105562.3	ENSP00000343001		O95155-1
UBE4B	ENST00000253251.12 linkuse as main transcript	c.809+665C>T		intron_variant		1		ENSP00000253251	P1	O95155-2
UBE4B	ENST00000672724.1 linkuse as main transcript	c.1022C>T	p.Ser341Phe	missense_variant	7/29			ENSP00000500453		O95155-4

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000209

AC:

AN:

248678

Hom.:

AF XY:

0.000178

AC XY:

AN XY:

134868

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00180

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000108

AC:

158

AN:

1461360

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000738

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000230

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000176

Hom.:

Bravo

AF:

0.000363

ESP6500AA

AF:

0.000240

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000182

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Nov 22, 2021

The c.1022C>T (p.S341F) alteration is located in exon 7 (coding exon 7) of the UBE4B gene. This alteration results from a C to T substitution at nucleotide position 1022, causing the serine (S) at amino acid position 341 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.47

M_CAP

Benign

0.0075

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.75

REVEL

Benign

0.082

Sift

Benign

0.12

Sift4G

Uncertain

0.032

Polyphen

0.35

Vest4

0.13

MVP

0.19

MPC

0.64

ClinPred

0.096

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.19

gMVP

0.30

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