Genetic Variant UBA6:p.Ala774Thr (chr4-67630474-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018227.6(UBA6):c.2320G>A(p.Ala774Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,433,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBA6
NM_018227.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.902

Publications

0 publications found

Variant links:

Genes affected

UBA6 (HGNC:25581): (ubiquitin like modifier activating enzyme 6) Modification of proteins with ubiquitin (UBB; MIM 191339) or ubiquitin-like proteins controls many signaling networks and requires a ubiquitin-activating enzyme (E1), a ubiquitin conjugating enzyme (E2), and a ubiquitin protein ligase (E3). UBE1L2 is an E1 enzyme that initiates the activation and conjugation of ubiquitin-like proteins (Jin et al., 2007 [PubMed 17597759]).[supplied by OMIM, Mar 2008]

UBA6 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

UBA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03170681).

BP6

Variant 4-67630474-C-T is Benign according to our data. Variant chr4-67630474-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3812749.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018227.6. 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
	UBA6	NM_018227.6	MANE Select	c.2320G>A	p.Ala774Thr	missense	Exon 26 of 33	NP_060697.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBA6	ENST00000322244.10	TSL:1 MANE Select	c.2320G>A	p.Ala774Thr	missense	Exon 26 of 33	ENSP00000313454.4	A0AVT1-1
UBA6	ENST00000907530.1		c.2338G>A	p.Ala780Thr	missense	Exon 27 of 34	ENSP00000577589.1
UBA6	ENST00000907528.1		c.2326G>A	p.Ala776Thr	missense	Exon 26 of 33	ENSP00000577587.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1433822

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32768

American (AMR)

AF:

0.00

AC:

AN:

41280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25274

East Asian (EAS)

AF:

0.00

AC:

AN:

39280

South Asian (SAS)

AF:

0.0000245

AC:

AN:

81714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097388

Other (OTH)

AF:

0.00

AC:

AN:

59174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.057

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.081

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.068

M_CAP

Benign

0.0035

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.8

PhyloP100

0.90

PrimateAI

Benign

0.36

PROVEAN

Benign

1.1

REVEL

Benign

0.057

Sift

Benign

0.84

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.099

MutPred

0.35

Gain of helix (P = 0.2684)

MVP

0.043

MPC

0.14

ClinPred

0.23

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.016

gMVP

0.10

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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