chr13-99238545-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_177967.4(UBAC2):​c.275C>T​(p.Thr92Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UBAC2
NM_177967.4 missense

Scores

15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.866
Variant links:
Genes affected
UBAC2 (HGNC:20486): (UBA domain containing 2) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of retrograde protein transport, ER to cytosol. Acts upstream of or within protein localization to endoplasmic reticulum. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.053666353).
BP6
Variant 13-99238545-C-T is Benign according to our data. Variant chr13-99238545-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3812784.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBAC2NM_001144072.2 linkc.150C>T p.Asn50Asn synonymous_variant Exon 2 of 9 ENST00000403766.8 NP_001137544.1 Q8NBM4-1A0A024RE02A8K2S7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBAC2ENST00000403766.8 linkc.150C>T p.Asn50Asn synonymous_variant Exon 2 of 9 2 NM_001144072.2 ENSP00000383911.3 Q8NBM4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250226
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135348
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1456220
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
2
AN XY:
724560
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:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Benign:1
Mar 05, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.038
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
1.4
DANN
Benign
0.95
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.054
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
-0.24
N
REVEL
Benign
0.018
Sift
Benign
0.056
T
Sift4G
Benign
0.27
T
Polyphen
0.24
B
Vest4
0.22
MutPred
0.33
Gain of catalytic residue at A97 (P = 0.0174);
MVP
0.13
ClinPred
0.061
T
GERP RS
-6.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs1271534240; hg19: chr13-99890799; API