21-42403987-C-T

Variant names:

• chr21-42403987-C-T
• rs779006157
• NM_018961.4:c.42C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018961.4(UBASH3A):​c.42C>T​(p.Asn14Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,375,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: UBASH3A NM_018961.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=2.33 with no splicing effect.

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.42C>T	p.Asn14Asn	synonymous	Exon 1 of 15	NP_061834.1	P57075-1
	UBASH3A	NM_001001895.3		c.42C>T	p.Asn14Asn	synonymous	Exon 1 of 14	NP_001001895.1	P57075-2
	UBASH3A	NM_001243467.2		c.42C>T	p.Asn14Asn	synonymous	Exon 1 of 12	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.42C>T	p.Asn14Asn	synonymous	Exon 1 of 15	ENSP00000317327.6	P57075-1
	UBASH3A	ENST00000291535.11	TSL:1	c.42C>T	p.Asn14Asn	synonymous	Exon 1 of 14	ENSP00000291535.6	P57075-2
	UBASH3A	ENST00000398367.1	TSL:1	c.42C>T	p.Asn14Asn	synonymous	Exon 1 of 12	ENSP00000381408.1	P57075-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1375192 Hom.: 0 Cov.: 28 AF XY: 0.00000147 AC XY: 1 AN XY: 678312

African (AFR) AF: 0.00 AC: 0 AN: 30276

American (AMR) AF: 0.0000294 AC: 1 AN: 33984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24634

East Asian (EAS) AF: 0.00 AC: 0 AN: 33886

South Asian (SAS) AF: 0.00 AC: 0 AN: 76228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4992

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1065464

Other (OTH) AF: 0.00 AC: 0 AN: 56832

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		2.3
PromoterAI		-0.068	Neutral

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

Other links and lift over

dbSNP: rs779006157; hg19: chr21-43824096;