22-32395164-C-G

Position:

• chr22-32395164-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.824

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

Verdict is Benign. Variant got -9 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_single_submitter, 1 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	UniProt
RTCB	NM_014306.5	c.1041G>C	p.Val347=	synonymous_variant	9/12	ENST00000216038.6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00512 AC: 779 AN: 152194 Hom.: 2 Cov.: 33

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.: 6 AF XY: 0.00603 AC XY: 819 AN XY: 135898

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.: 74 Cov.: 32 AF XY: 0.00882 AC XY: 6415 AN XY: 727230

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.: 2 Cov.: 33 AF XY: 0.00485 AC XY: 361 AN XY: 74484

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.: 6

Bravo AF: 0.00530

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00714

EpiControl AF: 0.0100

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 18, 2017

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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

Other links and lift over

dbSNP: rs41310258; hg19: chr22-32791151;