9-128309770-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015679.3(TRUB2):​c.776G>A​(p.Arg259His) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

TRUB2
NM_015679.3 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90
Variant links:
Genes affected
TRUB2 (HGNC:17170): (TruB pseudouridine synthase family member 2) Pseudouridine is an abundant component of rRNAs and tRNAs and is enzymatically generated by isomerization of uridine by pseudouridine synthase (Zucchini et al., 2003 [PubMed 12736709]).[supplied by OMIM, Mar 2008]
SWI5 (HGNC:31412): (SWI5 homologous recombination repair protein) Involved in cellular response to ionizing radiation and double-strand break repair via homologous recombination. Part of Swi5-Sfr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRUB2NM_015679.3 linkuse as main transcriptc.776G>A p.Arg259His missense_variant 8/8 ENST00000372890.6 NP_056494.1 O95900-1A0A024R886
TRUB2NM_001329861.2 linkuse as main transcriptc.644G>A p.Arg215His missense_variant 7/7 NP_001316790.1 O95900
TRUB2NM_001329862.2 linkuse as main transcriptc.608G>A p.Arg203His missense_variant 8/8 NP_001316791.1 O95900-2
TRUB2NM_001329863.2 linkuse as main transcriptc.464G>A p.Arg155His missense_variant 9/9 NP_001316792.1 O95900

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRUB2ENST00000372890.6 linkuse as main transcriptc.776G>A p.Arg259His missense_variant 8/81 NM_015679.3 ENSP00000361982.4 O95900-1
TRUB2ENST00000460320.1 linkuse as main transcriptn.856G>A non_coding_transcript_exon_variant 9/92
SWI5ENST00000652598.1 linkuse as main transcriptn.329-4060C>T intron_variant ENSP00000498805.2 A0A494C0Z4
TRUB2ENST00000461180.1 linkuse as main transcriptn.*14G>A downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
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
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251390
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135874
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727244
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:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 30, 2024The c.776G>A (p.R259H) alteration is located in exon 8 (coding exon 8) of the TRUB2 gene. This alteration results from a G to A substitution at nucleotide position 776, causing the arginine (R) at amino acid position 259 to be replaced by a histidine (H). 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
0.22
BayesDel_addAF
Uncertain
0.044
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Benign
-0.83
T
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.3
D
REVEL
Uncertain
0.31
Sift
Benign
0.063
T
Sift4G
Benign
0.064
T
Polyphen
0.99
D
Vest4
0.57
MutPred
0.63
Loss of MoRF binding (P = 0.0516);
MVP
0.27
MPC
0.48
ClinPred
0.94
D
GERP RS
5.7
Varity_R
0.26
gMVP
0.59

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: rs753214205; hg19: chr9-131072049; COSMIC: COSV65759163; COSMIC: COSV65759163; API