12-112406301-AAG-TAC

Variant names:

• chr12-112406301-AAG-TAC
• NM_000970.6:c.520_522delCTTinsGTA
• RPL6 p.Leu174Val

Variant summary

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

The NM_000970.6(RPL6):​c.520_522delCTTinsGTA​(p.Leu174Val) variant causes a missense change. 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. L174F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL6 NM_000970.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• Publications: 0 publications found

Genes affected

RPL6 (HGNC:10362): (ribosomal protein L6) This gene encodes a protein component of the 60S ribosomal subunit. This protein can bind specifically to domain C of the tax-responsive enhancer element of human T-cell leukemia virus type 1, and may participate in tax-mediated transactivation of transcription. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ENSG00000305485 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000970.6. 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
	RPL6	NM_000970.6	MANE Select	c.520_522delCTTinsGTA	p.Leu174Val	missense	N/A	NP_000961.2
	RPL6	NM_001024662.3		c.520_522delCTTinsGTA	p.Leu174Val	missense	N/A	NP_001019833.1	Q02878
	RPL6	NM_001320137.2		c.520_522delCTTinsGTA	p.Leu174Val	missense	N/A	NP_001307066.1	Q02878

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL6	ENST00000202773.14	TSL:1 MANE Select	c.520_522delCTTinsGTA	p.Leu174Val	missense	N/A	ENSP00000202773.9	Q02878
	RPL6	ENST00000424576.6	TSL:1	c.520_522delCTTinsGTA	p.Leu174Val	missense	N/A	ENSP00000403172.2	Q02878
	RPL6	ENST00000935343.1		c.598_600delCTTinsGTA	p.Leu200Val	missense	N/A	ENSP00000605402.1

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		6.0

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: chr12-112844105;