rs2231645

Positions:

• chr9-128309443-T-A
• chr9-128309443-T-C

Variant summary

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

The NM_015679.3(TRUB2):​c.*107A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,241,942 control chromosomes in the GnomAD database, including 33,069 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 0.31 (11599 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21470 hom.)
• Consequence: TRUB2 NM_015679.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRUB2	NM_015679.3	c.*107A>T		3_prime_UTR_variant	8/8	ENST00000372890.6	NP_056494.1
TRUB2	NM_001329861.2	c.*107A>T		3_prime_UTR_variant	7/7		NP_001316790.1
TRUB2	NM_001329862.2	c.*107A>T		3_prime_UTR_variant	8/8		NP_001316791.1
TRUB2	NM_001329863.2	c.*107A>T		3_prime_UTR_variant	9/9		NP_001316792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRUB2	ENST00000372890	c.*107A>T		3_prime_UTR_variant	8/8	1	NM_015679.3	ENSP00000361982.4
SWI5	ENST00000652598.1	n.329-4387T>A		intron_variant				ENSP00000498805.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47703 AN: 151766 Hom.: 11552 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.174 AC: 189522 AN: 1090058 Hom.: 21470 Cov.: 15 AF XY: 0.173 AC XY: 93691 AN XY: 542826

Gnomad4 AFR exome AF: 0.703

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.315 AC: 47802 AN: 151884 Hom.: 11599 Cov.: 32 AF XY: 0.312 AC XY: 23164 AN XY: 74258

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.273

Alfa AF: 0.223 Hom.: 815

Bravo AF: 0.336

Asia WGS AF: 0.297 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2231645; hg19: chr9-131071722;