21-42403801-A-C

Variant names:

• chr21-42403801-A-C
• rs2277797
• ENST00000635189.1:c.-30-115A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000635189.1(UBASH3A):​c.-30-115A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: UBASH3A ENST00000635189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635189.1. 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.-145A>C		upstream_gene	N/A	NP_061834.1
	UBASH3A	NM_001001895.3		c.-145A>C		upstream_gene	N/A	NP_001001895.1
	UBASH3A	NM_001243467.2		c.-145A>C		upstream_gene	N/A	NP_001230396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3A	ENST00000635189.1	TSL:4	c.-30-115A>C		intron	N/A	ENSP00000489058.1
	UBASH3A	ENST00000319294.11	TSL:1 MANE Select	c.-145A>C		upstream_gene	N/A	ENSP00000317327.6
	UBASH3A	ENST00000291535.11	TSL:1	c.-145A>C		upstream_gene	N/A	ENSP00000291535.6

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.58
PhyloP100		-1.1
PromoterAI		-0.021	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2277797; hg19: chr21-43823910;