rs7099565

Variant names:

• chr10-114959784-G-A
• rs7099565
• NM_139169.5:c.500G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_139169.5(TRUB1):​c.500G>A​(p.Arg167Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,598,310 control chromosomes in the GnomAD database, including 173,175 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.51 (22028 hom., cov: 32)
  • Exomes 𝑓: 0.45 (151147 hom.)
• Consequence: TRUB1 NM_139169.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

Genes affected

TRUB1 (HGNC:16060): (TruB pseudouridine synthase family member 1) 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRUB1	NM_139169.5	c.500G>A	p.Arg167Lys	missense_variant	Exon 4 of 8	ENST00000298746.5	NP_631908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRUB1	ENST00000298746.5	c.500G>A	p.Arg167Lys	missense_variant	Exon 4 of 8	1	NM_139169.5	ENSP00000298746.3
TRUB1	ENST00000485065.1	n.368G>A		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77564 AN: 151916 Hom.: 21986 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.0362

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.522

GnomAD3 exomes AF: 0.412 AC: 102998 AN: 250164 Hom.: 24289 AF XY: 0.413 AC XY: 55876 AN XY: 135252

Gnomad AFR exome AF: 0.751

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.0391

Gnomad SAS exome AF: 0.413

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.439

GnomAD4 exome AF: 0.446 AC: 644705 AN: 1446276 Hom.: 151147 Cov.: 30 AF XY: 0.444 AC XY: 320084 AN XY: 720288

Gnomad4 AFR exome AF: 0.747

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.0320

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.511 AC: 77659 AN: 152034 Hom.: 22028 Cov.: 32 AF XY: 0.502 AC XY: 37293 AN XY: 74320

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.526

Alfa AF: 0.474 Hom.: 32929

Bravo AF: 0.512

TwinsUK AF: 0.460 AC: 1706

ALSPAC AF: 0.472 AC: 1819

ESP6500AA AF: 0.739 AC: 3254

ESP6500EA AF: 0.461 AC: 3964

ExAC AF: 0.424 AC: 51522

Asia WGS AF: 0.290 AC: 1009 AN: 3478

EpiCase AF: 0.466

EpiControl AF: 0.468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.55
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.024	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.35	N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.085
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.28
ClinPred		0.0064	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.039
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7099565; hg19: chr10-116719543; COSMIC: COSV53929323;