16-1945585-CCACGG-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005061.3(RPL3L):​c.1076_1080del​(p.Ala359GlyfsTer4) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Consequence

RPL3L
NM_005061.3 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.99
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL3LNM_005061.3 linkuse as main transcriptc.1076_1080del p.Ala359GlyfsTer4 frameshift_variant 9/10 ENST00000268661.8
RPL3LXM_011522571.3 linkuse as main transcriptc.1091_1095del p.Ala364GlyfsTer4 frameshift_variant 9/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL3LENST00000268661.8 linkuse as main transcriptc.1076_1080del p.Ala359GlyfsTer4 frameshift_variant 9/101 NM_005061.3 P1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Cardiomyopathy, dilated, 2D Uncertain:1
Uncertain significance, criteria provided, single submitterresearchHudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for BiotechnologyJun 23, 2021ACMG codes: PM2; PP4 -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxFeb 05, 2024Identified with a second RPL3L variant in patients with neonatal-onset dilated cardiomyopathy referred for genetic testing at GeneDx and in published literature (PMID: 35323613); Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; This variant is associated with the following publications: (PMID: 35323613) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-1995586; API