2-95108245-CC-TT

Variant names:

• chr2-95108245-CC-TT
• NM_031902.5:c.566_567delGGinsAA
• MRPS5 p.Arg189Gln

Variant summary

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

The NM_031902.5(MRPS5):​c.566_567delGGinsAA​(p.Arg189Gln) variant causes a missense change involving the alteration of a non-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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R189W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPS5 NM_031902.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 0 publications found

Genes affected

MRPS5 (HGNC:14498): (mitochondrial ribosomal protein S5) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S5P family. Pseudogenes corresponding to this gene are found on chromosomes 4q, 5q, and 18q. [provided by RefSeq, Jul 2008]

ENSG00000289685 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031902.5. 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
	MRPS5	NM_031902.5	MANE Select	c.566_567delGGinsAA	p.Arg189Gln	missense	N/A	NP_114108.1	P82675-1
	MRPS5	NM_001321995.2		c.329_330delGGinsAA	p.Arg110Gln	missense	N/A	NP_001308924.1	A0A8Q3SIP9
	MRPS5	NM_001321996.2		c.139+8_139+9delGGinsAA		splice_region intron	N/A	NP_001308925.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS5	ENST00000272418.7	TSL:1 MANE Select	c.566_567delGGinsAA	p.Arg189Gln	missense	N/A	ENSP00000272418.2	P82675-1
	ENSG00000289685	ENST00000695456.1		n.*1445_*1446delGGinsAA		non_coding_transcript_exon	Exon 10 of 17	ENSP00000511928.1
	ENSG00000289685	ENST00000695456.1		n.*1445_*1446delGGinsAA		3_prime_UTR	Exon 10 of 17	ENSP00000511928.1

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

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: chr2-95773990;