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GeneBe

16-1945855-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_005061.3(RPL3L):c.1027C>T(p.Arg343Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RPL3L
NM_005061.3 missense

Scores

8
8
3

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.57
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 Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.956
PP5
Variant 16-1945855-G-A is Pathogenic according to our data. Variant chr16-1945855-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1162249.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL3LNM_005061.3 linkuse as main transcriptc.1027C>T p.Arg343Trp missense_variant 8/10 ENST00000268661.8
RPL3LXM_011522571.3 linkuse as main transcriptc.1042C>T p.Arg348Trp missense_variant 8/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL3LENST00000268661.8 linkuse as main transcriptc.1027C>T p.Arg343Trp missense_variant 8/101 NM_005061.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152160
Hom.:
0
Cov.:
32
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:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251232
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135814
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:
0.000163
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461656
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
727096
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:
0.00000989
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.0000113
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Cardiomyopathy, dilated, 2D Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJun 06, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
Cadd
Pathogenic
26
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T
Eigen
Uncertain
0.33
Eigen_PC
Benign
0.074
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Uncertain
0.025
D
MutationAssessor
Pathogenic
3.5
H
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Pathogenic
-7.2
D
REVEL
Uncertain
0.53
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.93
MutPred
0.87
Loss of MoRF binding (P = 0.102);
MVP
0.80
MPC
0.54
ClinPred
1.0
D
GERP RS
-0.41
Varity_R
0.89
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.62
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.62
Position offset: 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: rs1465045317; hg19: chr16-1995856; COSMIC: COSV51906414; COSMIC: COSV51906414; API