16-1947002-A-G

Variant names:

• chr16-1947002-A-G
• rs752624571
• NM_005061.3:c.785T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_005061.3(RPL3L):​c.785T>C​(p.Val262Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,611,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: RPL3L NM_005061.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.27

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL3L	NM_005061.3	c.785T>C	p.Val262Ala	missense_variant	Exon 6 of 10	ENST00000268661.8	NP_005052.1
RPL3L	XM_011522571.3	c.800T>C	p.Val267Ala	missense_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.785T>C	p.Val262Ala	missense_variant	Exon 6 of 10	1	NM_005061.3	ENSP00000268661.7

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152224 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000843 AC: 21 AN: 249106 AF XY: 0.0000814

Gnomad AFR exome AF: 0.0000623

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000234 AC: 341 AN: 1459516 Hom.: 0 Cov.: 32 AF XY: 0.000211 AC XY: 153 AN XY: 726036

Gnomad4 AFR exome AF: 0.0000299 AC: 1 AN: 33432

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44610

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26088

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39684

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86212

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52188

Gnomad4 NFE exome AF: 0.000276 AC: 307 AN: 1111592

Gnomad4 Remaining exome AF: 0.000547 AC: 33 AN: 60298

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152224 Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11 AN XY: 74364

Gnomad4 AFR AF: 0.0000965 AC: 0.0000964506 AN: 0.0000964506

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000250 AC: 0.000249919 AN: 0.000249919

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000198 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.0000495 AC: 6

EpiCase AF: 0.000545

EpiControl AF: 0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.785T>C (p.V262A) alteration is located in exon 6 (coding exon 6) of the RPL3L gene. This alteration results from a T to C substitution at nucleotide position 785, causing the valine (V) at amino acid position 262 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.97	D
Vest4		0.94
MVP		0.77
MPC		0.54
ClinPred		0.95	D
GERP RS		4.9
Varity_R		0.90
gMVP		0.84
Mutation Taster		=38/62	disease causing

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: rs752624571; hg19: chr16-1997003;