16-1947096-C-T

Variant names:

• chr16-1947096-C-T
• rs1157241329
• NM_005061.3:c.691G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005061.3(RPL3L):​c.691G>A​(p.Val231Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPL3L NM_005061.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.79

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL3L	NM_005061.3	c.691G>A	p.Val231Ile	missense_variant, splice_region_variant	Exon 6 of 10	ENST00000268661.8	NP_005052.1
RPL3L	XM_011522571.3	c.706G>A	p.Val236Ile	missense_variant, splice_region_variant	Exon 6 of 10		XP_011520873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL3L	ENST00000268661.8	c.691G>A	p.Val231Ile	missense_variant, splice_region_variant	Exon 6 of 10	1	NM_005061.3	ENSP00000268661.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250018 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135550

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461176 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726920

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.039	D
Polyphen		0.94	P
Vest4		0.76
MutPred		0.75		Loss of glycosylation at S233 (P = 0.0994);
MVP		0.81
MPC		0.28
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.67
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1157241329; hg19: chr16-1997097;