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GeneBe

16-1946677-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005061.3(RPL3L):c.899A>G(p.Lys300Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RPL3L
NM_005061.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0520
Variant links:
Genes affected
RPL3L (HGNC:10351): (ribosomal protein L3 like) This gene encodes a protein that shares sequence similarity with ribosomal protein L3. The protein belongs to the L3P family of ribosomal proteins. Unlike the ubiquitous expression of ribosomal protein genes, this gene has a tissue-specific pattern of expression, with the highest levels of expression in skeletal muscle and heart. It is not currently known whether the encoded protein is a functional ribosomal protein or whether it has evolved a function that is independent of the ribosome. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.104233).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL3LNM_005061.3 linkuse as main transcriptc.899A>G p.Lys300Arg missense_variant 7/10 ENST00000268661.8
RPL3LXM_011522571.3 linkuse as main transcriptc.914A>G p.Lys305Arg missense_variant 7/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL3LENST00000268661.8 linkuse as main transcriptc.899A>G p.Lys300Arg missense_variant 7/101 NM_005061.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152266
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249662
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135502
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1460482
Hom.:
0
Cov.:
33
AF XY:
0.00000963
AC XY:
7
AN XY:
726568
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152266
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

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 submitterclinical testingAmbry GeneticsMay 04, 2023The c.899A>G (p.K300R) alteration is located in exon 7 (coding exon 7) of the RPL3L gene. This alteration results from a A to G substitution at nucleotide position 899, causing the lysine (K) at amino acid position 300 to be replaced by an arginine (R). 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
Benign
0.065
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.66
Cadd
Benign
13
Dann
Uncertain
0.97
DEOGEN2
Benign
0.042
T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.33
N
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
0.91
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.10
Sift
Benign
0.075
T
Sift4G
Benign
0.074
T
Polyphen
0.0020
B
Vest4
0.12
MVP
0.40
MPC
0.094
ClinPred
0.17
T
GERP RS
-2.7
Varity_R
0.057
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs145900208; hg19: chr16-1996678; API