chr8-144790476-GGG-AGGGA

Position:

• chr8-144790476-GGG-AGGGA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001317782.2(RPL8):​c.500-8_500-6delCCCinsTCCCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL8 NM_001317782.2 splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0420

Genes affected

RPL8 (HGNC:10368): (ribosomal protein L8) 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 L2P family of ribosomal proteins. It is located in the cytoplasm. In rat, the protein associates with the 5.8S rRNA, very likely participates in the binding of aminoacyl-tRNA, and is a constituent of the elongation factor 2-binding site at the ribosomal subunit interface. Alternatively spliced transcript variants encoding the same protein exist. 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL8	NM_001317782.2	c.500-8_500-6delCCCinsTCCCT		splice_region_variant, intron_variant		ENST00000528957.6	NP_001304711.1
RPL8	NM_000973.5	c.500-8_500-6delCCCinsTCCCT		splice_region_variant, intron_variant			NP_000964.1
RPL8	NM_001317771.2	c.500-8_500-6delCCCinsTCCCT		splice_region_variant, intron_variant			NP_001304700.1
RPL8	NM_033301.3	c.500-8_500-6delCCCinsTCCCT		splice_region_variant, intron_variant			NP_150644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL8	ENST00000528957.6	c.500-8_500-6delCCCinsTCCCT		splice_region_variant, intron_variant		1	NM_001317782.2	ENSP00000433464.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Diamond-Blackfan anemia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

Nov 11, 2024

The RPL8 c.500-8_500-6delinsTCCCT intronic change results from deletion of GG and insertion of CCC and insertion of TCCCT at the -6 position in the intron 4 of the RPL8 gene. Algorithms that predict the impact of sequence changes on splicing indicate that this change does not impact splicing, but these predictions have not been confirmed by RNA studies. This variant is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). To our knowledge, this variant has not been reported in individuals with RPL8-associated conditions. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-146015861;