rs6585309

Variant names:

• chr10-114970578-G-A
• rs6585309
• NM_139169.5:c.596+138G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 rank	MANE	Protein	UniProt
TRUB1	NM_139169.5	c.596+138G>A		intron_variant	Intron 5 of 7	ENST00000298746.5	NP_631908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRUB1	ENST00000298746.5	c.596+138G>A		intron_variant	Intron 5 of 7	1	NM_139169.5	ENSP00000298746.3

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

African (AFR) AF: 0.744 AC: 10598 AN: 14238

American (AMR) AF: 0.229 AC: 6037 AN: 26306

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 6287 AN: 14792

East Asian (EAS) AF: 0.0304 AC: 1041 AN: 34196

South Asian (SAS) AF: 0.368 AC: 18099 AN: 49158

European-Finnish (FIN) AF: 0.360 AC: 13335 AN: 37000

Middle Eastern (MID) AF: 0.349 AC: 1037 AN: 2974

European-Non Finnish (NFE) AF: 0.398 AC: 125453 AN: 315078

Other (OTH) AF: 0.385 AC: 10954 AN: 28470

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

African (AFR) AF: 0.756 AC: 31395 AN: 41514

American (AMR) AF: 0.312 AC: 4768 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1532 AN: 3472

East Asian (EAS) AF: 0.0343 AC: 178 AN: 5186

South Asian (SAS) AF: 0.364 AC: 1756 AN: 4820

European-Finnish (FIN) AF: 0.343 AC: 3636 AN: 10586

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 27342 AN: 67962

Other (OTH) AF: 0.451 AC: 952 AN: 2110

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
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6585309; hg19: chr10-116730337;