rs2839511

Variant names:

• chr21-42428412-G-A
• rs2839511
• NM_018961.4:c.1170+1592G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 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.1170+1592G>A		intron	N/A	NP_061834.1	P57075-1
	UBASH3A	NM_001001895.3		c.1056+1592G>A		intron	N/A	NP_001001895.1	P57075-2
	UBASH3A	NM_001243467.2		c.1056+1592G>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.1170+1592G>A		intron	N/A	ENSP00000317327.6	P57075-1
	UBASH3A	ENST00000291535.11	TSL:1	c.1056+1592G>A		intron	N/A	ENSP00000291535.6	P57075-2
	UBASH3A	ENST00000398367.1	TSL:1	c.1056+1592G>A		intron	N/A	ENSP00000381408.1	P57075-3

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

African (AFR) AF: 0.0465 AC: 1928 AN: 41476

American (AMR) AF: 0.138 AC: 2111 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 866 AN: 3468

East Asian (EAS) AF: 0.0342 AC: 177 AN: 5168

South Asian (SAS) AF: 0.226 AC: 1082 AN: 4798

European-Finnish (FIN) AF: 0.162 AC: 1717 AN: 10572

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15091 AN: 67922

Other (OTH) AF: 0.175 AC: 369 AN: 2106

Alfa AF: 0.196 Hom.: 3075

Bravo AF: 0.147

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.49
PhyloP100		-3.3
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: rs2839511; hg19: chr21-43848521;