rs3788013

Variant names:

• chr21-42421219-C-A
• rs3788013
• NM_018961.4:c.1046+2610C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 54 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018961.4. 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
	UBASH3A	NM_018961.4	MANE Select	c.1046+2610C>A		intron	N/A	NP_061834.1	P57075-1
	UBASH3A	NM_001001895.3		c.932+2610C>A		intron	N/A	NP_001001895.1	P57075-2
	UBASH3A	NM_001243467.2		c.932+2610C>A		intron	N/A	NP_001230396.1	P57075-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3A	ENST00000319294.11	TSL:1 MANE Select	c.1046+2610C>A		intron	N/A	ENSP00000317327.6	P57075-1
	UBASH3A	ENST00000291535.11	TSL:1	c.932+2610C>A		intron	N/A	ENSP00000291535.6	P57075-2
	UBASH3A	ENST00000398367.1	TSL:1	c.932+2610C>A		intron	N/A	ENSP00000381408.1	P57075-3

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

African (AFR) AF: 0.534 AC: 22139 AN: 41434

American (AMR) AF: 0.381 AC: 5823 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1677 AN: 3472

East Asian (EAS) AF: 0.314 AC: 1619 AN: 5164

South Asian (SAS) AF: 0.311 AC: 1499 AN: 4820

European-Finnish (FIN) AF: 0.313 AC: 3309 AN: 10560

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28621 AN: 67974

Other (OTH) AF: 0.440 AC: 927 AN: 2108

Alfa AF: 0.428 Hom.: 45769

Bravo AF: 0.445

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.062
DANN	Benign	0.70
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3788013; hg19: chr21-43841328;