21-42403801-A-G

Variant summary

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

The ENST00000635189.1(UBASH3A):c.-30-115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 464,108 control chromosomes in the GnomAD database, including 35,955 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 0.41 (12958 hom., cov: 33)
  • Exomes 𝑓: 0.38 (22997 hom.)
• Consequence: UBASH3A ENST00000635189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBASH3A	ENST00000635189.1	c.-30-115A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61921 AN: 152030 Hom.: 12944 Cov.: 33

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.377 AC: 117655 AN: 311960 Hom.: 22997 AF XY: 0.374 AC XY: 60039 AN XY: 160586

Gnomad4 AFR exome AF: 0.437

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.407 AC: 61971 AN: 152148 Hom.: 12958 Cov.: 33 AF XY: 0.400 AC XY: 29752 AN XY: 74374

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.402

Alfa AF: 0.413 Hom.: 3302

Bravo AF: 0.408

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.31
Dann	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2277797; hg19: chr21-43823910;