rs5998473

Variant names:

• chr22-32395521-T-C
• rs5998473
• NM_014306.5:c.991-307A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014306.5(RTCB):​c.991-307A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,254 control chromosomes in the GnomAD database, including 748 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 0.083 (748 hom., cov: 32)
• Consequence: RTCB NM_014306.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999
• Publications: 2 publications found

Genes affected

RTCB (HGNC:26935): (RNA 2',3'-cyclic phosphate and 5'-OH ligase) Enables RNA ligase (ATP) activity and vinculin binding activity. Involved in tRNA splicing, via endonucleolytic cleavage and ligation. Located in cytosol and nucleoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014306.5. 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
	RTCB	NM_014306.5	MANE Select	c.991-307A>G		intron	N/A	NP_055121.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTCB	ENST00000216038.6	TSL:1 MANE Select	c.991-307A>G		intron	N/A	ENSP00000216038.5
	RTCB	ENST00000923680.1		c.1009-307A>G		intron	N/A	ENSP00000593739.1
	RTCB	ENST00000953018.1		c.1006-307A>G		intron	N/A	ENSP00000623077.1

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12556 AN: 152136 Hom.: 744 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0459

Gnomad OTH AF: 0.0576

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0826 AC: 12581 AN: 152254 Hom.: 748 Cov.: 32 AF XY: 0.0824 AC XY: 6134 AN XY: 74448

African (AFR) AF: 0.172 AC: 7128 AN: 41542

American (AMR) AF: 0.0467 AC: 715 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 167 AN: 3468

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5184

South Asian (SAS) AF: 0.0460 AC: 222 AN: 4828

European-Finnish (FIN) AF: 0.0930 AC: 985 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0459 AC: 3125 AN: 68028

Other (OTH) AF: 0.0570 AC: 120 AN: 2106

Alfa AF: 0.0711 Hom.: 97

Bravo AF: 0.0836

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.66
PhyloP100		-1.0
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: rs5998473; hg19: chr22-32791508;