17-76265920-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182565.4(UBALD2):​c.134C>T​(p.Thr45Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

UBALD2
NM_182565.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20
Variant links:
Genes affected
UBALD2 (HGNC:28438): (UBA like domain containing 2)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30521291).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBALD2NM_182565.4 linkc.134C>T p.Thr45Met missense_variant Exon 2 of 3 ENST00000327490.8 NP_872371.1 Q8IYN6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBALD2ENST00000327490.8 linkc.134C>T p.Thr45Met missense_variant Exon 2 of 3 1 NM_182565.4 ENSP00000331298.6 Q8IYN6

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1452730
Hom.:
0
Cov.:
33
AF XY:
0.00000139
AC XY:
1
AN XY:
721810
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 30, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.134C>T (p.T45M) alteration is located in exon 2 (coding exon 2) of the UBALD2 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the threonine (T) at amino acid position 45 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.050
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
T
Eigen
Benign
0.12
Eigen_PC
Benign
0.11
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.82
T
M_CAP
Pathogenic
0.50
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.91
N
REVEL
Benign
0.097
Sift
Benign
0.11
T
Sift4G
Benign
0.17
T
Polyphen
0.99
D
Vest4
0.34
MutPred
0.23
Loss of glycosylation at S44 (P = 0.0342);
MVP
0.26
MPC
1.4
ClinPred
0.75
D
GERP RS
2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.071
gMVP
0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-74262001; API