Variant chr22-32406709-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014306.5(RTCB):c.293A>G(p.Asn98Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RTCB
NM_014306.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.96

Variant links:

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]

RTCB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTCB	NM_014306.5 linkuse as main transcript	c.293A>G	p.Asn98Ser	missense_variant	4/12	ENST00000216038.6	NP_055121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RTCB	ENST00000216038.6 linkuse as main transcript	c.293A>G	p.Asn98Ser	missense_variant	4/12	1	NM_014306.5	ENSP00000216038	P1
RTCB	ENST00000476619.5 linkuse as main transcript	n.174A>G		non_coding_transcript_exon_variant	2/5	4
RTCB	ENST00000485373.5 linkuse as main transcript	n.150A>G		non_coding_transcript_exon_variant	2/5	4
RTCB	ENST00000487704.5 linkuse as main transcript	n.378A>G		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460706

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.293A>G (p.N98S) alteration is located in exon 4 (coding exon 4) of the RTCB gene. This alteration results from a A to G substitution at nucleotide position 293, causing the asparagine (N) at amino acid position 98 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

0.0047

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.60

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.18

Sift

Uncertain

0.019

Sift4G

Uncertain

0.046

Polyphen

0.34

Vest4

0.83

MutPred

0.72

Gain of sheet (P = 0.0344);

MVP

0.34

MPC

0.83

ClinPred

0.94

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.27

gMVP

0.86

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over