17-39201253-CG-AT

Variant names:

• chr17-39201253-CG-AT
• rs2046286330
• NM_000981.4:c.46_47delCGinsAT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM1 PP3

The NM_000981.4(RPL19):​c.46_47delCGinsAT​(p.Arg16Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R16C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPL19 NM_000981.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81
• Publications: 0 publications found

Genes affected

RPL19 (HGNC:10312): (ribosomal protein L19) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L19E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ENSG00000299210 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a modified_residue Citrulline (size 0) in uniprot entity RL19_HUMAN
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000981.4. 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
	RPL19	NM_000981.4	MANE Select	c.46_47delCGinsAT	p.Arg16Ile	missense	N/A	NP_000972.1	P84098
	RPL19	NM_001330200.1		c.40_41delCGinsAT	p.Arg14Ile	missense	N/A	NP_001317129.1	J3KTE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL19	ENST00000225430.9	TSL:1 MANE Select	c.46_47delCGinsAT	p.Arg16Ile	missense	N/A	ENSP00000225430.4	P84098
	RPL19	ENST00000678573.1		c.106_107delCGinsAT	p.Arg36Ile	missense	N/A	ENSP00000503598.1	A0A7I2YQG2
	RPL19	ENST00000869076.1		c.46_47delCGinsAT	p.Arg16Ile	missense	N/A	ENSP00000539135.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2046286330; hg19: chr17-37357506;