21-42416077-G-A

Position:

• chr21-42416077-G-A

Variant summary

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

The ENST00000319294.11(UBASH3A):​c.668-365G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,014 control chromosomes in the GnomAD database, including 6,631 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 0.28 (6631 hom., cov: 32)
• Consequence: UBASH3A ENST00000319294.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBASH3A	NM_018961.4	c.668-365G>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.668-365G>A		intron_variant		1	NM_018961.4	ENSP00000317327

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41880 AN: 151896 Hom.: 6628 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.276 AC: 41890 AN: 152014 Hom.: 6631 Cov.: 32 AF XY: 0.269 AC XY: 19959 AN XY: 74286

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.0350

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.318

Alfa AF: 0.350 Hom.: 21696

Bravo AF: 0.270

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.61
DANN	Benign	0.89

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: rs11203203; hg19: chr21-43836186;