2-95108246-C-G

Variant names:

• chr2-95108246-C-G
• NM_031902.5:c.566G>C

Variant summary

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

The NM_031902.5(MRPS5):​c.566G>C​(p.Arg189Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R189Q) 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

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

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 rank	MANE	Protein	UniProt
MRPS5	NM_031902.5	c.566G>C	p.Arg189Pro	missense_variant	Exon 5 of 12	ENST00000272418.7	NP_114108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS5	ENST00000272418.7	c.566G>C	p.Arg189Pro	missense_variant	Exon 5 of 12	1	NM_031902.5	ENSP00000272418.2
ENSG00000289685	ENST00000695456.1	n.*1445G>C		non_coding_transcript_exon_variant	Exon 10 of 17			ENSP00000511928.1
ENSG00000289685	ENST00000695456.1	n.*1445G>C		3_prime_UTR_variant	Exon 10 of 17			ENSP00000511928.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.057
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.20
Sift	Benign	0.27	T
Sift4G	Benign	0.32	T
Polyphen		0.86	P
Vest4		0.66
MutPred		0.37		Loss of helix (P = 0.0558);
MVP		0.45
MPC		0.45
ClinPred		0.86	D
GERP RS		3.3
Varity_R		0.069
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr2-95773991;