12-112405306-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000970.6(RPL6):​c.785A>C​(p.Lys262Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,610,990 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RPL6
NM_000970.6 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21
Variant links:
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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPL6NM_000970.6 linkc.785A>C p.Lys262Thr missense_variant Exon 7 of 7 ENST00000202773.14 NP_000961.2 Q02878A0A024RBK3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPL6ENST00000202773.14 linkc.785A>C p.Lys262Thr missense_variant Exon 7 of 7 1 NM_000970.6 ENSP00000202773.9 Q02878
RPL6ENST00000424576.6 linkc.785A>C p.Lys262Thr missense_variant Exon 7 of 7 1 ENSP00000403172.2 Q02878
RPL6ENST00000553205.1 linkn.783A>C non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000122
AC:
3
AN:
246800
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000268
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1458774
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
725800
show subpopulations
Gnomad4 AFR exome
AF:
0.00
AC:
0
AN:
33280
Gnomad4 AMR exome
AF:
0.00
AC:
0
AN:
44102
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
26114
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
39680
Gnomad4 SAS exome
AF:
0.00
AC:
0
AN:
85874
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
53398
Gnomad4 NFE exome
AF:
0.00000540
AC:
6
AN:
1111188
Gnomad4 Remaining exome
AF:
0.00
AC:
0
AN:
60214
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
AC:
0
AN:
0
Gnomad4 AMR
AF:
0.00
AC:
0
AN:
0
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.0000294
AC:
0.0000293988
AN:
0.0000293988
Gnomad4 OTH
AF:
0.00
AC:
0
AN:
0
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 04, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.785A>C (p.K262T) alteration is located in exon 7 (coding exon 6) of the RPL6 gene. This alteration results from a A to C substitution at nucleotide position 785, causing the lysine (K) at amino acid position 262 to be replaced by a threonine (T). 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
Uncertain
0.059
T
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.80
.;T
M_CAP
Benign
0.080
D
MetaRNN
Uncertain
0.51
D;D
MetaSVM
Benign
-0.48
T
MutationAssessor
Pathogenic
3.2
M;M
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.28
Sift
Uncertain
0.022
D;D
Sift4G
Uncertain
0.024
D;D
Polyphen
0.89
P;P
Vest4
0.38
MutPred
0.62
Loss of methylation at K262 (P = 0.0115);Loss of methylation at K262 (P = 0.0115);
MVP
0.55
MPC
2.1
ClinPred
0.95
D
GERP RS
5.2
Varity_R
0.40
gMVP
0.59
Mutation Taster
=27/73
disease causing

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: rs1473277975; hg19: chr12-112843110; API