rs3788013

Positions:

• chr21-42421219-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018961.4(UBASH3A):​c.1046+2610C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,020 control chromosomes in the GnomAD database, including 14,907 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 0.43 (14907 hom., cov: 32)
• Consequence: UBASH3A NM_018961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBASH3A	NM_018961.4	c.1046+2610C>A		intron_variant		ENST00000319294.11	NP_061834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBASH3A	ENST00000319294.11	c.1046+2610C>A		intron_variant		1	NM_018961.4	ENSP00000317327

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66034 AN: 151902 Hom.: 14886 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.442

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 66102 AN: 152020 Hom.: 14907 Cov.: 32 AF XY: 0.424 AC XY: 31520 AN XY: 74298

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.440

Alfa AF: 0.424 Hom.: 18085

Bravo AF: 0.445

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.062
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs3788013; hg19: chr21-43841328;