Genetic Variant UBASH3A:c.-30-115A>G (chr21-42403801-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000635189.1(UBASH3A):c.-30-115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 464,108 control chromosomes in the GnomAD database, including 35,955 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 0.41 ( 12958 hom., cov: 33)

Exomes 𝑓: 0.38 ( 22997 hom. )

Consequence

UBASH3A
ENST00000635189.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

6 publications found

Variant links:

Genes affected

UBASH3A (HGNC:12462): (ubiquitin associated and SH3 domain containing A) This gene encodes one of two family members belonging to the T-cell ubiquitin ligand (TULA) family. Both family members can negatively regulate T-cell signaling. This family member can facilitate growth factor withdrawal-induced apoptosis in T cells, which may occur via its interaction with AIF, an apoptosis-inducing factor. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

UBASH3A links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635189.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UBASH3A	NM_018961.4	MANE Select	c.-145A>G	upstream_gene	N/A	NP_061834.1
UBASH3A	NM_001001895.3		c.-145A>G	upstream_gene	N/A	NP_001001895.1
UBASH3A	NM_001243467.2		c.-145A>G	upstream_gene	N/A	NP_001230396.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UBASH3A	ENST00000635189.1	TSL:4	c.-30-115A>G	intron	N/A	ENSP00000489058.1
UBASH3A	ENST00000319294.11	TSL:1 MANE Select	c.-145A>G	upstream_gene	N/A	ENSP00000317327.6
UBASH3A	ENST00000291535.11	TSL:1	c.-145A>G	upstream_gene	N/A	ENSP00000291535.6

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61921

AN:

152030

Hom.:

12944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.403

GnomAD4 exome

AF:

0.377

AC:

117655

AN:

311960

Hom.:

22997

AF XY:

0.374

AC XY:

60039

AN XY:

160586

show subpopulations

African (AFR)

AF:

0.437

AC:

3458

AN:

7922

American (AMR)

AF:

0.279

AC:

2721

AN:

9768

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

3233

AN:

9986

East Asian (EAS)

AF:

0.442

AC:

10338

AN:

23378

South Asian (SAS)

AF:

0.260

AC:

3946

AN:

15172

European-Finnish (FIN)

AF:

0.346

AC:

13105

AN:

37928

Middle Eastern (MID)

AF:

0.332

AC:

476

AN:

1432

European-Non Finnish (NFE)

AF:

0.390

AC:

73213

AN:

187808

Other (OTH)

AF:

0.386

AC:

7165

AN:

18566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3103

6206

9310

12413

15516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.407

AC:

61971

AN:

152148

Hom.:

12958

Cov.:

AF XY:

0.400

AC XY:

29752

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.446

AC:

18490

AN:

41490

American (AMR)

AF:

0.340

AC:

5195

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1180

AN:

3468

East Asian (EAS)

AF:

0.468

AC:

2419

AN:

5174

South Asian (SAS)

AF:

0.396

AC:

1910

AN:

4826

European-Finnish (FIN)

AF:

0.341

AC:

3608

AN:

10594

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.410

AC:

27874

AN:

67978

Other (OTH)

AF:

0.402

AC:

849

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1933

3866

5800

7733

9666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.411

Hom.:

5155

Bravo

AF:

0.408

Asia WGS

AF:

0.398

AC:

1384

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.31

(source)

DANN

Benign

0.52

PhyloP100

-1.1

PromoterAI

0.0058

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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