16-1947005-C-T

Variant names:

• chr16-1947005-C-T
• rs370640499
• NM_005061.3:c.782G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005061.3(RPL3L):​c.782G>A​(p.Arg261His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,611,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: RPL3L NM_005061.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86
• Publications: 2 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), PanelApp Australia, Ambry Genetics
• dilated cardiomyopathy

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL3L	NM_005061.3	MANE Select	c.782G>A	p.Arg261His	missense	Exon 6 of 10	NP_005052.1	Q92901

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL3L	ENST00000268661.8	TSL:1 MANE Select	c.782G>A	p.Arg261His	missense	Exon 6 of 10	ENSP00000268661.7	Q92901
	RPL3L	ENST00000968104.1		c.857G>A	p.Arg286His	missense	Exon 6 of 10	ENSP00000638163.1
	RPL3L	ENST00000968108.1		c.842G>A	p.Arg281His	missense	Exon 7 of 11	ENSP00000638167.1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152258 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000205 AC: 51 AN: 249044 AF XY: 0.000237

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000711

Gnomad FIN exome AF: 0.0000471

Gnomad NFE exome AF: 0.000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000143 AC: 208 AN: 1459534 Hom.: 0 Cov.: 33 AF XY: 0.000160 AC XY: 116 AN XY: 726050

African (AFR) AF: 0.0000897 AC: 3 AN: 33440

American (AMR) AF: 0.0000673 AC: 3 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26084

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39684

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86212

European-Finnish (FIN) AF: 0.0000383 AC: 2 AN: 52158

Middle Eastern (MID) AF: 0.000184 AC: 1 AN: 5446

European-Non Finnish (NFE) AF: 0.000113 AC: 126 AN: 1111606

Other (OTH) AF: 0.000249 AC: 15 AN: 60302

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152258 Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 16 AN XY: 74394

African (AFR) AF: 0.000169 AC: 7 AN: 41476

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000156 Hom.: 0

Bravo AF: 0.000215

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000247 AC: 30

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.42
Sift	Benign	0.19	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.88
MVP		0.73
MPC		0.15
ClinPred		0.32	T
GERP RS		4.0
Varity_R		0.25
gMVP		0.82
Mutation Taster		=61/39	polymorphism

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: rs370640499; hg19: chr16-1997006; COSMIC: COSV51906347; COSMIC: COSV51906347;