Genetic Variant NM_014235.5:c.247G>C (chrX-154485887-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014235.5(UBL4A):c.247G>C(p.Glu83Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,209,764 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000011 ( 0 hom. 7 hem. )

Consequence

UBL4A
NM_014235.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.01

Publications

0 publications found

Variant links:

Genes affected

UBL4A (HGNC:12505): (ubiquitin like 4A) Enables chaperone binding activity. Involved in tail-anchored membrane protein insertion into ER membrane. Located in cytosol; membrane; and nucleoplasm. Part of BAT3 complex. [provided by Alliance of Genome Resources, Apr 2022]

UBL4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06235367).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014235.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBL4A	NM_014235.5	MANE Select	c.247G>C	p.Glu83Gln	missense	Exon 3 of 4	NP_055050.1	P11441

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBL4A	ENST00000369660.9	TSL:1 MANE Select	c.247G>C	p.Glu83Gln	missense	Exon 3 of 4	ENSP00000358674.4	P11441
UBL4A	ENST00000369653.8	TSL:3	c.247G>C	p.Glu83Gln	missense	Exon 3 of 5	ENSP00000358667.4	Q5HY81
UBL4A	ENST00000417913.1	TSL:5	n.*39G>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000397223.1	F8WB70

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112223

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000378

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000498

AC:

AN:

180564

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1097541

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363013

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26394

American (AMR)

AF:

0.00

AC:

AN:

35155

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19362

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54115

European-Finnish (FIN)

AF:

0.0000249

AC:

AN:

40132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4127

European-Non Finnish (NFE)

AF:

0.0000107

AC:

AN:

841978

Other (OTH)

AF:

0.0000434

AC:

AN:

46072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112223

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34395

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30897

American (AMR)

AF:

0.00

AC:

AN:

10748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3576

South Asian (SAS)

AF:

0.00

AC:

AN:

2747

European-Finnish (FIN)

AF:

0.000161

AC:

AN:

6213

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000378

AC:

AN:

52971

Other (OTH)

AF:

0.00

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.037

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.82

M_CAP

Benign

0.0051

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-3.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.090

REVEL

Benign

0.0020

Sift

Benign

0.18

Sift4G

Benign

0.16

Polyphen

0.0010

Vest4

0.090

MutPred

0.30

Loss of disorder (P = 0.1663)

MVP

0.52

MPC

0.49

ClinPred

0.060

GERP RS

-8.8

Varity_R

0.070

gMVP

0.45

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over