dbSNP rs2277798: UBASH3A:p.Ser18Gly (chr21-42403997-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 NM_018961.4(UBASH3A):c.52A>G(p.Ser18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,518,038 control chromosomes in the GnomAD database, including 297,364 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 27325 hom., cov: 32)

Exomes 𝑓: 0.63 ( 270039 hom. )

Consequence

UBASH3A
NM_018961.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.849

Publications

47 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:

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 (MetaRNN=2.6113288E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBASH3A	NM_018961.4 link	c.52A>G	p.Ser18Gly	missense_variant	Exon 1 of 15	ENST00000319294.11	NP_061834.1	P57075-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBASH3A	ENST00000319294.11 link	c.52A>G	p.Ser18Gly	missense_variant	Exon 1 of 15	1	NM_018961.4	ENSP00000317327.6		P57075-1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90453

AN:

151944

Hom.:

27304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.656

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.650

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.648

Gnomad OTH

AF:

0.607

GnomAD2 exomes

AF:

0.546

AC:

74867

AN:

137142

AF XY:

0.555

show subpopulations

Gnomad AFR exome

AF:

0.515

Gnomad AMR exome

AF:

0.388

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.539

Gnomad NFE exome

AF:

0.625

Gnomad OTH exome

AF:

0.573

GnomAD4 exome

AF:

0.625

AC:

853861

AN:

1365976

Hom.:

270039

Cov.:

AF XY:

0.624

AC XY:

420455

AN XY:

673308

show subpopulations

African (AFR)

AF:

0.559

AC:

16735

AN:

29946

American (AMR)

AF:

0.415

AC:

13752

AN:

33148

Ashkenazi Jewish (ASJ)

AF:

0.649

AC:

15839

AN:

24412

East Asian (EAS)

AF:

0.440

AC:

14688

AN:

33390

South Asian (SAS)

AF:

0.553

AC:

41255

AN:

74576

European-Finnish (FIN)

AF:

0.548

AC:

26570

AN:

48488

Middle Eastern (MID)

AF:

0.642

AC:

3147

AN:

4900

European-Non Finnish (NFE)

AF:

0.648

AC:

687270

AN:

1060664

Other (OTH)

AF:

0.613

AC:

34605

AN:

56452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

14894

29788

44682

59576

74470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18454

36908

55362

73816

92270

<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:

0.595

AC:

90515

AN:

152062

Hom.:

27325

Cov.:

AF XY:

0.585

AC XY:

43444

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.572

AC:

23735

AN:

41506

American (AMR)

AF:

0.511

AC:

7814

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.650

AC:

2255

AN:

3470

East Asian (EAS)

AF:

0.472

AC:

2431

AN:

5150

South Asian (SAS)

AF:

0.553

AC:

2668

AN:

4822

European-Finnish (FIN)

AF:

0.525

AC:

5553

AN:

10574

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.648

AC:

43998

AN:

67942

Other (OTH)

AF:

0.603

AC:

1273

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1899

3798

5697

7596

9495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<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:

0.630

Hom.:

115825

Bravo

AF:

0.591

TwinsUK

AF:

0.643

AC:

2384

ALSPAC

AF:

0.651

AC:

2508

ESP6500AA

AF:

0.576

AC:

2467

ESP6500EA

AF:

0.651

AC:

5382

ExAC

AF:

0.463

AC:

39832

Asia WGS

AF:

0.481

AC:

1670

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.022

T;.;T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.043

T;T;T;T

MetaRNN

Benign

0.000026

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.81

.;N;N;N

PhyloP100

0.85

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.55

.;N;N;N

REVEL

Benign

0.057

Sift

Benign

0.96

.;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.070, 0.030, 0.074

MPC

0.12

ClinPred

0.0047

GERP RS

3.4

PromoterAI

-0.0048

Neutral

(source)

Varity_R

0.049

gMVP

0.18

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over