12-112405899-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000970.6(RPL6):c.668G>A(p.Arg223Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,832 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00027 ( 1 hom. )
Consequence
RPL6
NM_000970.6 missense
NM_000970.6 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 7.34
Genes affected
RPL6 (HGNC:10362): (ribosomal protein L6) This gene encodes a protein component of the 60S ribosomal subunit. This protein can bind specifically to domain C of the tax-responsive enhancer element of human T-cell leukemia virus type 1, and may participate in tax-mediated transactivation of transcription. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19468418).
BS2
?
High AC in GnomAd4 at 40 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL6 | NM_000970.6 | c.668G>A | p.Arg223Gln | missense_variant | 6/7 | ENST00000202773.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL6 | ENST00000202773.14 | c.668G>A | p.Arg223Gln | missense_variant | 6/7 | 1 | NM_000970.6 | P1 | |
RPL6 | ENST00000424576.6 | c.668G>A | p.Arg223Gln | missense_variant | 6/7 | 1 | P1 | ||
RPL6 | ENST00000553205.1 | n.190G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152112Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
40
AN:
152112
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000201 AC: 50AN: 248202Hom.: 1 AF XY: 0.000223 AC XY: 30AN XY: 134600
GnomAD3 exomes
AF:
AC:
50
AN:
248202
Hom.:
AF XY:
AC XY:
30
AN XY:
134600
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000274 AC: 400AN: 1461602Hom.: 1 Cov.: 31 AF XY: 0.000271 AC XY: 197AN XY: 727108
GnomAD4 exome
AF:
AC:
400
AN:
1461602
Hom.:
Cov.:
31
AF XY:
AC XY:
197
AN XY:
727108
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000263 AC: 40AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74420
GnomAD4 genome
?
AF:
AC:
40
AN:
152230
Hom.:
Cov.:
33
AF XY:
AC XY:
15
AN XY:
74420
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
4
ExAC
?
AF:
AC:
21
EpiCase
AF:
EpiControl
AF:
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 | Dec 13, 2023 | The c.668G>A (p.R223Q) alteration is located in exon 6 (coding exon 5) of the RPL6 gene. This alteration results from a G to A substitution at nucleotide position 668, causing the arginine (R) at amino acid position 223 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
1.0
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at