Variant 21-42434957-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018961.4(UBASH3A):c.1393+3A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,522 control chromosomes in the GnomAD database, including 64,482 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4537 hom., cov: 33)

Exomes 𝑓: 0.28 ( 59945 hom. )

Consequence

UBASH3A
NM_018961.4 splice_region, intron

Scores

Splicing: ADA: 0.8002

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.697

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:

UBASH3A (HGNC:):

UBASH3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 21-42434957-A-C is Benign according to our data. Variant chr21-42434957-A-C is described in ClinVar as [Benign]. Clinvar id is 1232058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBASH3A	NM_018961.4 linkuse as main transcript	c.1393+3A>C		splice_region_variant, intron_variant		ENST00000319294.11	NP_061834.1	P57075-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBASH3A	ENST00000319294.11 linkuse as main transcript	c.1393+3A>C		splice_region_variant, intron_variant		1	NM_018961.4	ENSP00000317327.6		P57075-1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33986

AN:

152074

Hom.:

4532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0734

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.200

GnomAD3 exomes

AF:

0.269

AC:

67438

AN:

251092

Hom.:

9910

AF XY:

0.267

AC XY:

36260

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.0946

Gnomad EAS exome

AF:

0.276

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.281

AC:

410426

AN:

1461330

Hom.:

59945

Cov.:

AF XY:

0.279

AC XY:

202769

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.0603

Gnomad4 AMR exome

AF:

0.342

Gnomad4 ASJ exome

AF:

0.0997

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.258

Gnomad4 FIN exome

AF:

0.319

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.255

GnomAD4 genome

AF:

0.223

AC:

34008

AN:

152192

Hom.:

4537

Cov.:

AF XY:

0.227

AC XY:

16882

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0732

Gnomad4 AMR

AF:

0.281

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.264

Gnomad4 FIN

AF:

0.331

Gnomad4 NFE

AF:

0.287

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.251

Hom.:

7946

Bravo

AF:

0.213

Asia WGS

AF:

0.256

AC:

894

AN:

3478

EpiCase

AF:

0.260

EpiControl

AF:

0.262

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 23, 2019	This variant is associated with the following publications: (PMID: 29491471) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.5

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.80

dbscSNV1_RF

Benign

0.53

SpliceAI score (max)

0.53

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.53

Position offset: 26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over