21-42403967-CTC-GTT

Variant names:

• chr21-42403967-CTC-GTT
• NM_018961.4:c.22_24delCTCinsGTT
• UBASH3A p.Leu8Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018961.4(UBASH3A):​c.22_24delCTCinsGTT​(p.Leu8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L8I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UBASH3A NM_018961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3A	NM_018961.4	MANE Select	c.22_24delCTCinsGTT	p.Leu8Val	missense	N/A	NP_061834.1	P57075-1
	UBASH3A	NM_001001895.3		c.22_24delCTCinsGTT	p.Leu8Val	missense	N/A	NP_001001895.1	P57075-2
	UBASH3A	NM_001243467.2		c.22_24delCTCinsGTT	p.Leu8Val	missense	N/A	NP_001230396.1	P57075-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3A	ENST00000319294.11	TSL:1 MANE Select	c.22_24delCTCinsGTT	p.Leu8Val	missense	N/A	ENSP00000317327.6	P57075-1
	UBASH3A	ENST00000291535.11	TSL:1	c.22_24delCTCinsGTT	p.Leu8Val	missense	N/A	ENSP00000291535.6	P57075-2
	UBASH3A	ENST00000398367.1	TSL:1	c.22_24delCTCinsGTT	p.Leu8Val	missense	N/A	ENSP00000381408.1	P57075-3

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
PhyloP100		3.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-43824076;