chr10-114959784-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 13/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 46 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139169.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRUB1	NM_139169.5	MANE Select	c.500G>A	p.Arg167Lys	missense	Exon 4 of 8	NP_631908.1	Q8WWH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRUB1	ENST00000298746.5	TSL:1 MANE Select	c.500G>A	p.Arg167Lys	missense	Exon 4 of 8	ENSP00000298746.3	Q8WWH5
	TRUB1	ENST00000948779.1		c.500G>A	p.Arg167Lys	missense	Exon 4 of 8	ENSP00000618838.1
	TRUB1	ENST00000900222.1		c.497G>A	p.Arg166Lys	missense	Exon 4 of 8	ENSP00000570281.1

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

GnomAD2 exomes AF: 0.412 AC: 102998 AN: 250164 AF XY: 0.413

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 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

African (AFR) AF: 0.747 AC: 24698 AN: 33068

American (AMR) AF: 0.263 AC: 11711 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 13538 AN: 26024

East Asian (EAS) AF: 0.0320 AC: 1268 AN: 39630

South Asian (SAS) AF: 0.416 AC: 35554 AN: 85564

European-Finnish (FIN) AF: 0.436 AC: 23252 AN: 53376

Middle Eastern (MID) AF: 0.516 AC: 2961 AN: 5734

European-Non Finnish (NFE) AF: 0.460 AC: 504965 AN: 1098396

Other (OTH) AF: 0.447 AC: 26758 AN: 59912

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

African (AFR) AF: 0.749 AC: 31049 AN: 41462

American (AMR) AF: 0.365 AC: 5587 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3466

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5176

South Asian (SAS) AF: 0.402 AC: 1933 AN: 4814

European-Finnish (FIN) AF: 0.423 AC: 4466 AN: 10566

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 31018 AN: 67944

Other (OTH) AF: 0.526 AC: 1113 AN: 2116

Alfa AF: 0.474 Hom.: 73640

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 v4.9

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
PhyloP100		2.6
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
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

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