chr9-135501045-C-A

Variant names:

• chr9-135501045-C-A
• NM_016034.5:c.91C>A

Variant summary

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

The NM_016034.5(MRPS2):​c.91C>A​(p.Pro31Thr) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P31P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRPS2 NM_016034.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.486
• Publications: 0 publications found

Genes affected

MRPS2 (HGNC:14495): (mitochondrial ribosomal protein S2) 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 S2 family. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

PIERCE1 (HGNC:28435): (piercer of microtubule wall 1) Predicted to act upstream of or within several processes, including cellular response to DNA damage stimulus; cellular response to UV-C; and determination of left/right symmetry. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12721407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016034.5. 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
	MRPS2	NM_016034.5	MANE Select	c.91C>A	p.Pro31Thr	missense	Exon 2 of 4	NP_057118.1	Q9Y399
	MRPS2	NM_001371401.1		c.91C>A	p.Pro31Thr	missense	Exon 3 of 5	NP_001358330.1	Q9Y399
	MRPS2	NR_051967.3		n.120C>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS2	ENST00000241600.10	TSL:1 MANE Select	c.91C>A	p.Pro31Thr	missense	Exon 2 of 4	ENSP00000241600.5	Q9Y399
	PIERCE1	ENST00000371791.5	TSL:1	c.-65+584G>T		intron	N/A	ENSP00000360856.1	Q5BN46-2
	MRPS2	ENST00000371785.5	TSL:3	c.91C>A	p.Pro31Thr	missense	Exon 3 of 5	ENSP00000360850.1	Q9Y399

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	Benign	0.080
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.6
DANN	Benign	0.86
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.49
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.0060
Sift	Benign	0.13	T
Sift4G	Benign	0.088	T
Polyphen		0.041	B
Vest4		0.29
MVP		0.38
MPC		0.25
ClinPred		0.061	T
GERP RS		-1.5
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.034
gMVP		0.41
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr9-138392891;