NM_031902.5:c.1026G>T

Variant names:

• chr2-95090428-C-A
• NM_031902.5:c.1026G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031902.5(MRPS5):​c.1026G>T​(p.Met342Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPS5 NM_031902.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.819
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22798753).

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.1026G>T	p.Met342Ile	missense	Exon 11 of 12	NP_114108.1	P82675-1
	MRPS5	NM_001321995.2		c.789G>T	p.Met263Ile	missense	Exon 11 of 12	NP_001308924.1	A0A8Q3SIP9
	MRPS5	NM_001321996.2		c.528G>T	p.Met176Ile	missense	Exon 11 of 12	NP_001308925.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS5	ENST00000272418.7	TSL:1 MANE Select	c.1026G>T	p.Met342Ile	missense	Exon 11 of 12	ENSP00000272418.2	P82675-1
	ENSG00000289685	ENST00000695456.1		n.*1905G>T		non_coding_transcript_exon	Exon 16 of 17	ENSP00000511928.1
	ENSG00000289685	ENST00000695456.1		n.*1905G>T		3_prime_UTR	Exon 16 of 17	ENSP00000511928.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.82
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.073
Sift	Benign	0.37	T
Sift4G	Benign	0.24	T
Polyphen		0.014	B
Vest4		0.39
MutPred		0.60		Loss of MoRF binding (P = 0.1316)
MVP		0.44
MPC		0.23
ClinPred		0.39	T
GERP RS		4.1
Varity_R		0.087
gMVP		0.49
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr2-95756173; COSMIC: COSV55534355;