21-42416281-A-G

Variant names:

• chr21-42416281-A-G
• rs9976767
• NM_018961.4:c.668-161A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018961.4(UBASH3A):​c.668-161A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,706 control chromosomes in the GnomAD database, including 15,634 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 0.45 (15634 hom., cov: 30)
• Consequence: UBASH3A NM_018961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546
• Publications: 59 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3A	NM_018961.4	MANE Select	c.668-161A>G		intron	N/A	NP_061834.1
	UBASH3A	NM_001001895.3		c.554-161A>G		intron	N/A	NP_001001895.1
	UBASH3A	NM_001243467.2		c.554-161A>G		intron	N/A	NP_001230396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3A	ENST00000319294.11	TSL:1 MANE Select	c.668-161A>G		intron	N/A	ENSP00000317327.6
	UBASH3A	ENST00000291535.11	TSL:1	c.554-161A>G		intron	N/A	ENSP00000291535.6
	UBASH3A	ENST00000398367.1	TSL:1	c.554-161A>G		intron	N/A	ENSP00000381408.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67775 AN: 151588 Hom.: 15613 Cov.: 30

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.447 AC: 67843 AN: 151706 Hom.: 15634 Cov.: 30 AF XY: 0.436 AC XY: 32338 AN XY: 74114

African (AFR) AF: 0.533 AC: 22029 AN: 41336

American (AMR) AF: 0.393 AC: 5994 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1694 AN: 3466

East Asian (EAS) AF: 0.313 AC: 1609 AN: 5146

South Asian (SAS) AF: 0.338 AC: 1618 AN: 4786

European-Finnish (FIN) AF: 0.328 AC: 3441 AN: 10506

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30003 AN: 67912

Other (OTH) AF: 0.458 AC: 964 AN: 2106

Alfa AF: 0.444 Hom.: 46759

Bravo AF: 0.456

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.19
PhyloP100		-0.55
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: rs9976767; hg19: chr21-43836390; COSMIC: COSV52311981; COSMIC: COSV52311981;