16-1947613-A-G

Variant names:

• chr16-1947613-A-G
• rs2252523
• NM_005061.3:c.502-233T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005061.3(RPL3L):​c.502-233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,096 control chromosomes in the GnomAD database, including 37,187 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (37187 hom., cov: 33)
• Consequence: RPL3L NM_005061.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654
• Publications: 9 publications found

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]

RPL3L Gene-Disease associations (from GenCC):

• cardiomyopathy, dilated, 2D

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL3L	NM_005061.3	c.502-233T>C		intron_variant	Intron 4 of 9	ENST00000268661.8	NP_005052.1
RPL3L	XM_011522571.3	c.517-233T>C		intron_variant	Intron 4 of 9		XP_011520873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL3L	ENST00000268661.8	c.502-233T>C		intron_variant	Intron 4 of 9	1	NM_005061.3	ENSP00000268661.7

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105768 AN: 151978 Hom.: 37155 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.699

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.696 AC: 105844 AN: 152096 Hom.: 37187 Cov.: 33 AF XY: 0.699 AC XY: 51964 AN XY: 74338

African (AFR) AF: 0.685 AC: 28415 AN: 41492

American (AMR) AF: 0.601 AC: 9190 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2692 AN: 3472

East Asian (EAS) AF: 0.716 AC: 3696 AN: 5164

South Asian (SAS) AF: 0.887 AC: 4278 AN: 4824

European-Finnish (FIN) AF: 0.679 AC: 7174 AN: 10558

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48040 AN: 67990

Other (OTH) AF: 0.703 AC: 1483 AN: 2110

Alfa AF: 0.708 Hom.: 75071

Bravo AF: 0.681

Asia WGS AF: 0.805 AC: 2801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.46
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2252523; hg19: chr16-1997614;