19-48615438-GAC-CAG

Variant names:

• chr19-48615438-GAC-CAG
• NM_000979.4:c.499_501delGTCinsCTG
• RPL18 p.Val167Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_000979.4(RPL18):​c.499_501delGTCinsCTG​(p.Val167Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V167I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL18 NM_000979.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.38
• Publications: 0 publications found

Genes affected

RPL18 (HGNC:10310): (ribosomal protein L18) 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 member of the L18E family of ribosomal proteins that is a component of the 60S subunit. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

RPL18 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 18

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• 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_000979.4. 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
	RPL18	NM_000979.4	MANE Select	c.499_501delGTCinsCTG	p.Val167Leu	missense	N/A	NP_000970.1	Q07020-1
	RPL18	NM_001270490.2		c.412_414delGTCinsCTG	p.Val138Leu	missense	N/A	NP_001257419.1	Q07020-2
	RPL18	NR_073022.2		n.526_528delGTCinsCTG		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL18	ENST00000549920.6	TSL:1 MANE Select	c.499_501delGTCinsCTG	p.Val167Leu	missense	N/A	ENSP00000447001.1	Q07020-1
	RPL18	ENST00000084795.9	TSL:1	c.502_504delGTCinsCTG	p.Val168Leu	missense	N/A	ENSP00000084795.5	J3QQ67
	RPL18	ENST00000919794.1		c.490_492delGTCinsCTG	p.Val164Leu	missense	N/A	ENSP00000589853.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-49118695;