rs773952076

Variant names:

• chr21-42404013-C-A
• rs773952076
• NM_018961.4:c.68C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-42404013-C-A
• chr21-42404013-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018961.4(UBASH3A):​c.68C>A​(p.Ser23*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000798 in 1,377,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000080 (0 hom.)
• Consequence: UBASH3A NM_018961.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.68C>A	p.Ser23*	stop_gained	Exon 1 of 15	NP_061834.1	P57075-1
	UBASH3A	NM_001001895.3		c.68C>A	p.Ser23*	stop_gained	Exon 1 of 14	NP_001001895.1	P57075-2
	UBASH3A	NM_001243467.2		c.68C>A	p.Ser23*	stop_gained	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.68C>A	p.Ser23*	stop_gained	Exon 1 of 15	ENSP00000317327.6	P57075-1
	UBASH3A	ENST00000291535.11	TSL:1	c.68C>A	p.Ser23*	stop_gained	Exon 1 of 14	ENSP00000291535.6	P57075-2
	UBASH3A	ENST00000398367.1	TSL:1	c.68C>A	p.Ser23*	stop_gained	Exon 1 of 12	ENSP00000381408.1	P57075-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000700 AC: 1 AN: 142850 AF XY: 0.0000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000798 AC: 11 AN: 1377626 Hom.: 0 Cov.: 36 AF XY: 0.0000103 AC XY: 7 AN XY: 679438

African (AFR) AF: 0.00 AC: 0 AN: 30412

American (AMR) AF: 0.00 AC: 0 AN: 34162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24750

East Asian (EAS) AF: 0.00 AC: 0 AN: 34076

South Asian (SAS) AF: 0.00 AC: 0 AN: 76530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4964

European-Non Finnish (NFE) AF: 0.0000103 AC: 11 AN: 1066808

Other (OTH) AF: 0.00 AC: 0 AN: 56988

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000103 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	35
DANN	Benign	0.96
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.32	N
PhyloP100		0.16
Vest4		0.39
GERP RS		2.5
PromoterAI		-0.025	Neutral
Mutation Taster		=16/184	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs773952076; hg19: chr21-43824122;