1-44777694-AAG-CAA

Variant names:

• chr1-44777694-AAG-CAA
• NM_001012.2:c.292_294delAAGinsCAA
• RPS8 p.Lys98Gln

Variant summary

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

The NM_001012.2(RPS8):​c.292_294delAAGinsCAA​(p.Lys98Gln) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS8 NM_001012.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.82
• Publications: 0 publications found

Genes affected

RPS8 (HGNC:10441): (ribosomal protein S8) 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 40S subunit. The protein belongs to the S8E family of ribosomal proteins. It is located in the cytoplasm. Increased expression of this gene in colorectal tumors and colon polyps compared to matched normal colonic mucosa has been observed. This gene is co-transcribed with the small nucleolar RNA genes U38A, U38B, U39, and U40, which are located in its fourth, fifth, first, and second introns, respectively. 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]

SNORD38A (HGNC:30355): (small nucleolar RNA, C/D box 38A)

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_001012.2. 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
	RPS8	NM_001012.2	MANE Select	c.292_294delAAGinsCAA	p.Lys98Gln	missense	N/A	NP_001003.1	P62241
	SNORD38A	NR_001456.1		n.-148_-146delAAGinsCAA		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS8	ENST00000396651.8	TSL:1 MANE Select	c.292_294delAAGinsCAA	p.Lys98Gln	missense	N/A	ENSP00000379888.3	P62241
	RPS8	ENST00000485390.5	TSL:1	n.686_688delAAGinsCAA		non_coding_transcript_exon	Exon 3 of 5
	RPS8	ENST00000932906.1		c.295_297delAAGinsCAA	p.Lys99Gln	missense	N/A	ENSP00000602965.1

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		8.8

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: chr1-45243366;