16-1945588-C-G

Variant names:

• chr16-1945588-C-G
• rs140116056
• NM_005061.3:c.1078G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005061.3(RPL3L):​c.1078G>C​(p.Val360Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RPL3L NM_005061.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026470184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL3L	NM_005061.3	c.1078G>C	p.Val360Leu	missense_variant	Exon 9 of 10	ENST00000268661.8	NP_005052.1
RPL3L	XM_011522571.3	c.1093G>C	p.Val365Leu	missense_variant	Exon 9 of 10		XP_011520873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL3L	ENST00000268661.8	c.1078G>C	p.Val360Leu	missense_variant	Exon 9 of 10	1	NM_005061.3	ENSP00000268661.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 251084 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135828

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

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: 0.00000274 AC: 4 AN: 1461688 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727132

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.9
DANN	Benign	0.49
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.9	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.35		Loss of methylation at R357 (P = 0.1222);
MVP		0.28
MPC		0.10
ClinPred		0.024	T
GERP RS		2.9
Varity_R		0.063
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs140116056; hg19: chr16-1995589;