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GeneBe

22-32396236-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_014306.5(RTCB):c.828T>C(p.Ala276=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,614,104 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 22 hom., cov: 33)
Exomes 𝑓: 0.0020 ( 31 hom. )

Consequence

RTCB
NM_014306.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.990
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-32396236-A-G is Benign according to our data. Variant chr22-32396236-A-G is described in ClinVar as [Benign]. Clinvar id is 786379.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.99 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1783/152312) while in subpopulation AFR AF= 0.0351 (1461/41570). AF 95% confidence interval is 0.0336. There are 22 homozygotes in gnomad4. There are 839 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RTCBNM_014306.5 linkuse as main transcriptc.828T>C p.Ala276= synonymous_variant 8/12 ENST00000216038.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RTCBENST00000216038.6 linkuse as main transcriptc.828T>C p.Ala276= synonymous_variant 8/121 NM_014306.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0117
AC:
1779
AN:
152194
Hom.:
22
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0352
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0126
Gnomad ASJ
AF:
0.00577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.00112
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00399
AC:
1003
AN:
251242
Hom.:
7
AF XY:
0.00312
AC XY:
423
AN XY:
135770
show subpopulations
Gnomad AFR exome
AF:
0.0346
Gnomad AMR exome
AF:
0.00590
Gnomad ASJ exome
AF:
0.00626
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00121
Gnomad OTH exome
AF:
0.00587
GnomAD4 exome
AF:
0.00205
AC:
2996
AN:
1461792
Hom.:
31
Cov.:
31
AF XY:
0.00187
AC XY:
1360
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.0351
Gnomad4 AMR exome
AF:
0.00684
Gnomad4 ASJ exome
AF:
0.00544
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000881
Gnomad4 OTH exome
AF:
0.00523
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0117
AC:
1783
AN:
152312
Hom.:
22
Cov.:
33
AF XY:
0.0113
AC XY:
839
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0351
Gnomad4 AMR
AF:
0.0126
Gnomad4 ASJ
AF:
0.00577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00112
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00619
Hom.:
8
Bravo
AF:
0.0140
Asia WGS
AF:
0.00346
AC:
12
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
9.6
Dann
Benign
0.62

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.

Other links and lift over

dbSNP: rs10222228; hg19: chr22-32792223; API