Genetic Variant UBASH3A:p.Leu24Phe (chr21-42404015-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018961.4(UBASH3A):c.70C>T(p.Leu24Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 1,526,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

UBASH3A
NM_018961.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0120

Publications

0 publications found

Variant links:

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]

UBASH3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 (MetaRNN=0.04014924).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBASH3A	NM_018961.4	MANE Select	c.70C>T	p.Leu24Phe	missense	Exon 1 of 15	NP_061834.1	P57075-1
UBASH3A	NM_001001895.3		c.70C>T	p.Leu24Phe	missense	Exon 1 of 14	NP_001001895.1	P57075-2
UBASH3A	NM_001243467.2		c.70C>T	p.Leu24Phe	missense	Exon 1 of 12	NP_001230396.1	P57075-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBASH3A	ENST00000319294.11	TSL:1 MANE Select	c.70C>T	p.Leu24Phe	missense	Exon 1 of 15	ENSP00000317327.6	P57075-1
UBASH3A	ENST00000291535.11	TSL:1	c.70C>T	p.Leu24Phe	missense	Exon 1 of 14	ENSP00000291535.6	P57075-2
UBASH3A	ENST00000398367.1	TSL:1	c.70C>T	p.Leu24Phe	missense	Exon 1 of 12	ENSP00000381408.1	P57075-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000142

AC:

AN:

141078

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000215

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.28e-7

AC:

AN:

1374484

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

677846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30252

American (AMR)

AF:

0.00

AC:

AN:

33902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24678

East Asian (EAS)

AF:

0.0000296

AC:

AN:

33840

South Asian (SAS)

AF:

0.00

AC:

AN:

76288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4946

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1064886

Other (OTH)

AF:

0.00

AC:

AN:

56836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000312

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.78

M_CAP

Benign

0.011

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

PhyloP100

-0.012

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

REVEL

Benign

0.027

Sift

Benign

0.048

Sift4G

Pathogenic

0.0

Polyphen

0.20

Vest4

0.18

MutPred

0.51

Loss of loop (P = 0.0603)

MVP

0.32

MPC

0.20

ClinPred

0.10

GERP RS

2.5

PromoterAI

0.0020

Neutral

(source)

Varity_R

0.054

gMVP

0.37

Mutation Taster

=87/13

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over