rs7283281

chr21-42405410-G-Cchr21-42405410-G-Achr21-42405410-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.114-898G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,964 control chromosomes in the GnomAD database, including 18,777 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 0.49 (18777 hom., cov: 32)
• Consequence: UBASH3A NM_018961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBASH3A	NM_018961.4	c.114-898G>C		intron_variant		ENST00000319294.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBASH3A	ENST00000319294.11	c.114-898G>C		intron_variant		1	NM_018961.4

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74873 AN: 151846 Hom.: 18759 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.493 AC: 74936 AN: 151964 Hom.: 18777 Cov.: 32 AF XY: 0.483 AC XY: 35881 AN XY: 74272

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.492

Alfa AF: 0.377 Hom.: 1063

Bravo AF: 0.494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.27

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: rs7283281; hg19: chr21-43825519;