rs2277798

Variant names:

• chr21-42403997-A-G
• rs2277798
• NM_018961.4:c.52A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018961.4(UBASH3A):​c.52A>G​(p.Ser18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,518,038 control chromosomes in the GnomAD database, including 297,364 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27325 hom., cov: 32)
  • Exomes 𝑓: 0.63 (270039 hom.)
• Consequence: UBASH3A NM_018961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849
• Publications: 48 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.6113288E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

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.52A>G	p.Ser18Gly	missense	Exon 1 of 15	NP_061834.1	P57075-1
	UBASH3A	NM_001001895.3		c.52A>G	p.Ser18Gly	missense	Exon 1 of 14	NP_001001895.1	P57075-2
	UBASH3A	NM_001243467.2		c.52A>G	p.Ser18Gly	missense	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.52A>G	p.Ser18Gly	missense	Exon 1 of 15	ENSP00000317327.6	P57075-1
	UBASH3A	ENST00000291535.11	TSL:1	c.52A>G	p.Ser18Gly	missense	Exon 1 of 14	ENSP00000291535.6	P57075-2
	UBASH3A	ENST00000398367.1	TSL:1	c.52A>G	p.Ser18Gly	missense	Exon 1 of 12	ENSP00000381408.1	P57075-3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90453 AN: 151944 Hom.: 27304 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.607

GnomAD2 exomes AF: 0.546 AC: 74867 AN: 137142 AF XY: 0.555

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.400

Gnomad FIN exome AF: 0.539

Gnomad NFE exome AF: 0.625

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.625 AC: 853861 AN: 1365976 Hom.: 270039 Cov.: 43 AF XY: 0.624 AC XY: 420455 AN XY: 673308

African (AFR) AF: 0.559 AC: 16735 AN: 29946

American (AMR) AF: 0.415 AC: 13752 AN: 33148

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 15839 AN: 24412

East Asian (EAS) AF: 0.440 AC: 14688 AN: 33390

South Asian (SAS) AF: 0.553 AC: 41255 AN: 74576

European-Finnish (FIN) AF: 0.548 AC: 26570 AN: 48488

Middle Eastern (MID) AF: 0.642 AC: 3147 AN: 4900

European-Non Finnish (NFE) AF: 0.648 AC: 687270 AN: 1060664

Other (OTH) AF: 0.613 AC: 34605 AN: 56452

GnomAD4 genome AF: 0.595 AC: 90515 AN: 152062 Hom.: 27325 Cov.: 32 AF XY: 0.585 AC XY: 43444 AN XY: 74326

African (AFR) AF: 0.572 AC: 23735 AN: 41506

American (AMR) AF: 0.511 AC: 7814 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2255 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2431 AN: 5150

South Asian (SAS) AF: 0.553 AC: 2668 AN: 4822

European-Finnish (FIN) AF: 0.525 AC: 5553 AN: 10574

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 43998 AN: 67942

Other (OTH) AF: 0.603 AC: 1273 AN: 2110

Alfa AF: 0.630 Hom.: 115825

Bravo AF: 0.591

TwinsUK AF: 0.643 AC: 2384

ALSPAC AF: 0.651 AC: 2508

ESP6500AA AF: 0.576 AC: 2467

ESP6500EA AF: 0.651 AC: 5382

ExAC AF: 0.463 AC: 39832

Asia WGS AF: 0.481 AC: 1670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.043	T
MetaRNN	Benign	0.000026	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.81	N
PhyloP100		0.85
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.057
Sift	Benign	0.96	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.070
MPC		0.12
ClinPred		0.0047	T
GERP RS		3.4
PromoterAI		-0.0048	Neutral
Varity_R		0.049
gMVP		0.18
Mutation Taster		=96/4	polymorphism (auto)

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: rs2277798; hg19: chr21-43824106; COSMIC: COSV52311938;