rs2839511

Positions:

• chr21-42428412-G-A
• chr21-42428412-G-T

Variant summary

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

The NM_018961.4(UBASH3A):​c.1170+1592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,998 control chromosomes in the GnomAD database, including 2,366 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 0.16 (2366 hom., cov: 31)
• Consequence: UBASH3A NM_018961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBASH3A	NM_018961.4	c.1170+1592G>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.1170+1592G>A		intron_variant		1	NM_018961.4	ENSP00000317327.6

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23601 AN: 151880 Hom.: 2365 Cov.: 31

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0344

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.155 AC: 23594 AN: 151998 Hom.: 2366 Cov.: 31 AF XY: 0.153 AC XY: 11347 AN XY: 74288

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0342

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.175

Alfa AF: 0.200 Hom.: 1945

Bravo AF: 0.147

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.49

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: rs2839511; hg19: chr21-43848521;