Genetic Variant UBA6:c.1037+337G>C (chr4-67662802-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018227.6(UBA6):c.1037+337G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 185,828 control chromosomes in the GnomAD database, including 13,684 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 11197 hom., cov: 33)

Exomes 𝑓: 0.37 ( 2487 hom. )

Consequence

UBA6
NM_018227.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.456

Publications

4 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

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.1037+337G>C		intron	N/A	NP_060697.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UBA6	ENST00000322244.10	TSL:1 MANE Select	c.1037+337G>C	intron	N/A	ENSP00000313454.4	A0AVT1-1
UBA6	ENST00000420827.2	TSL:1	c.1037+337G>C	intron	N/A	ENSP00000399234.2	A0AVT1-3
UBA6	ENST00000907530.1		c.1037+337G>C	intron	N/A	ENSP00000577589.1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

57964

AN:

151864

Hom.:

11185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.378

GnomAD4 exome

AF:

0.370

AC:

12533

AN:

33844

Hom.:

2487

Cov.:

AF XY:

0.366

AC XY:

6451

AN XY:

17616

show subpopulations

African (AFR)

AF:

0.366

AC:

343

AN:

936

American (AMR)

AF:

0.331

AC:

662

AN:

2002

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

483

AN:

1156

East Asian (EAS)

AF:

0.294

AC:

537

AN:

1824

South Asian (SAS)

AF:

0.307

AC:

701

AN:

2282

European-Finnish (FIN)

AF:

0.395

AC:

492

AN:

1244

Middle Eastern (MID)

AF:

0.375

AC:

AN:

112

European-Non Finnish (NFE)

AF:

0.383

AC:

8517

AN:

22238

Other (OTH)

AF:

0.369

AC:

756

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

370

740

1110

1480

1850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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

AF:

0.382

AC:

58011

AN:

151984

Hom.:

11197

Cov.:

AF XY:

0.380

AC XY:

28224

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.368

AC:

15242

AN:

41440

American (AMR)

AF:

0.364

AC:

5561

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

1470

AN:

3468

East Asian (EAS)

AF:

0.320

AC:

1655

AN:

5166

South Asian (SAS)

AF:

0.321

AC:

1548

AN:

4820

European-Finnish (FIN)

AF:

0.393

AC:

4138

AN:

10532

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.396

AC:

26909

AN:

67970

Other (OTH)

AF:

0.375

AC:

792

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1870

3740

5609

7479

9349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.220

Hom.:

448

Bravo

AF:

0.383

Asia WGS

AF:

0.303

AC:

1055

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.078

(source)

DANN

Benign

0.47

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over