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GeneBe

21-42413101-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_018961.4(UBASH3A):c.432G>T(p.Thr144=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,192 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00064 ( 8 hom. )

Consequence

UBASH3A
NM_018961.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.24
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 21-42413101-G-T is Benign according to our data. Variant chr21-42413101-G-T is described in ClinVar as [Benign]. Clinvar id is 730924.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.24 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000642 (939/1461892) while in subpopulation AFR AF= 0.0168 (564/33480). AF 95% confidence interval is 0.0157. There are 8 homozygotes in gnomad4_exome. There are 473 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBASH3ANM_018961.4 linkuse as main transcriptc.432G>T p.Thr144= synonymous_variant 4/15 ENST00000319294.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBASH3AENST00000319294.11 linkuse as main transcriptc.432G>T p.Thr144= synonymous_variant 4/151 NM_018961.4 P57075-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00477
AC:
726
AN:
152182
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0155
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00340
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00151
AC:
379
AN:
251476
Hom.:
3
AF XY:
0.00132
AC XY:
180
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.0162
Gnomad AMR exome
AF:
0.000954
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00193
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000105
Gnomad OTH exome
AF:
0.00179
GnomAD4 exome
AF:
0.000642
AC:
939
AN:
1461892
Hom.:
8
Cov.:
31
AF XY:
0.000650
AC XY:
473
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0168
Gnomad4 AMR exome
AF:
0.00112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000414
Gnomad4 OTH exome
AF:
0.00157
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00476
AC:
725
AN:
152300
Hom.:
4
Cov.:
32
AF XY:
0.00461
AC XY:
343
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0154
Gnomad4 AMR
AF:
0.00340
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00232
Hom.:
0
Bravo
AF:
0.00569
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 11, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
0.14
Dann
Benign
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61733938; hg19: chr21-43833210; API