rs6585309

Positions:

• chr10-114970578-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139169.5(TRUB1):​c.596+138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 674,352 control chromosomes in the GnomAD database, including 59,647 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.

• Frequency:
  • Genomes: 𝑓 0.47 (19756 hom., cov: 33)
  • Exomes 𝑓: 0.37 (39891 hom.)
• Consequence: TRUB1 NM_139169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRUB1	NM_139169.5	c.596+138G>A		intron_variant		ENST00000298746.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRUB1	ENST00000298746.5	c.596+138G>A		intron_variant		1	NM_139169.5	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71856 AN: 152022 Hom.: 19714 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.369 AC: 192841 AN: 522212 Hom.: 39891 AF XY: 0.369 AC XY: 103180 AN XY: 279314

Gnomad4 AFR exome AF: 0.744

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.0304

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.398

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.473 AC: 71949 AN: 152140 Hom.: 19756 Cov.: 33 AF XY: 0.463 AC XY: 34404 AN XY: 74368

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.0343

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.451

Alfa AF: 0.433 Hom.: 3243

Bravo AF: 0.479

Asia WGS AF: 0.274 AC: 954 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs6585309; hg19: chr10-116730337;