rs1003904

Variant names:

• chr16-1946074-G-A
• rs1003904
• NM_005061.3:c.952-144C>T

Variant summary

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

The NM_005061.3(RPL3L):​c.952-144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 636,792 control chromosomes in the GnomAD database, including 61,350 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 0.45 (16421 hom., cov: 33)
  • Exomes 𝑓: 0.42 (44929 hom.)
• Consequence: RPL3L NM_005061.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005061.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL3L	NM_005061.3	MANE Select	c.952-144C>T		intron	N/A	NP_005052.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL3L	ENST00000268661.8	TSL:1 MANE Select	c.952-144C>T		intron	N/A	ENSP00000268661.7

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68886 AN: 151978 Hom.: 16394 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.417 AC: 202210 AN: 484696 Hom.: 44929 AF XY: 0.428 AC XY: 109460 AN XY: 255602

African (AFR) AF: 0.580 AC: 7645 AN: 13182

American (AMR) AF: 0.373 AC: 7082 AN: 18978

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 6412 AN: 13940

East Asian (EAS) AF: 0.583 AC: 18424 AN: 31598

South Asian (SAS) AF: 0.607 AC: 29796 AN: 49126

European-Finnish (FIN) AF: 0.381 AC: 11681 AN: 30674

Middle Eastern (MID) AF: 0.380 AC: 1337 AN: 3518

European-Non Finnish (NFE) AF: 0.366 AC: 108391 AN: 296448

Other (OTH) AF: 0.420 AC: 11442 AN: 27232

GnomAD4 genome AF: 0.453 AC: 68950 AN: 152096 Hom.: 16421 Cov.: 33 AF XY: 0.458 AC XY: 34051 AN XY: 74334

African (AFR) AF: 0.581 AC: 24118 AN: 41494

American (AMR) AF: 0.410 AC: 6270 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1576 AN: 3470

East Asian (EAS) AF: 0.584 AC: 3018 AN: 5164

South Asian (SAS) AF: 0.617 AC: 2973 AN: 4822

European-Finnish (FIN) AF: 0.387 AC: 4088 AN: 10574

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25527 AN: 67962

Other (OTH) AF: 0.433 AC: 913 AN: 2110

Alfa AF: 0.402 Hom.: 24878

Bravo AF: 0.451

Asia WGS AF: 0.594 AC: 2064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.078
DANN	Benign	0.45
PhyloP100		-1.3
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: rs1003904; hg19: chr16-1996075;