Variant 22-32395164-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_014306.5(RTCB):c.1041G>C(p.Val347=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00849 in 1,614,178 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0088 ( 74 hom. )

Consequence

RTCB
NM_014306.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.824

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 22-32395164-C-G is Benign according to our data. Variant chr22-32395164-C-G is described in ClinVar as [Benign]. Clinvar id is 782754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.824 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTCB	NM_014306.5 linkuse as main transcript	c.1041G>C	p.Val347=	synonymous_variant	9/12	ENST00000216038.6	NP_055121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTCB	ENST00000216038.6 linkuse as main transcript	c.1041G>C	p.Val347=	synonymous_variant	9/12	1	NM_014306.5	ENSP00000216038	P1

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

779

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00897

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00553

AC:

1391

AN:

251456

Hom.:

AF XY:

0.00603

AC XY:

819

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.000979

Gnomad SAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.00898

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00884

AC:

12929

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00882

AC XY:

6415

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.00366

Gnomad4 FIN exome

AF:

0.00241

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00598

GnomAD4 genome

AF:

0.00511

AC:

779

AN:

152312

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00897

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00831

Hom.:

Bravo

AF:

0.00530

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00714

EpiControl

AF:

0.0100

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

5.2

DANN

Benign

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over