2-105089066-C-G

Position:

• chr2-105089066-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182640.3(MRPS9):​c.572C>G​(p.Thr191Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRPS9 NM_182640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.626

Genes affected

MRPS9 (HGNC:14501): (mitochondrial ribosomal protein S9) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079809695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS9	NM_182640.3	c.572C>G	p.Thr191Ser	missense_variant	6/11	ENST00000258455.8	NP_872578.1
MRPS9	XM_011511644.3	c.200C>G	p.Thr67Ser	missense_variant	5/10		XP_011509946.1
MRPS9	XM_047445533.1	c.572C>G	p.Thr191Ser	missense_variant	6/7		XP_047301489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS9	ENST00000258455.8	c.572C>G	p.Thr191Ser	missense_variant	6/11	1	NM_182640.3	ENSP00000258455.3
MRPS9	ENST00000413583.5	n.47C>G		non_coding_transcript_exon_variant	1/6	3		ENSP00000388885.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.572C>G (p.T191S) alteration is located in exon 6 (coding exon 6) of the MRPS9 gene. This alteration results from a C to G substitution at nucleotide position 572, causing the threonine (T) at amino acid position 191 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.071
DANN	Benign	0.37
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.56	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.68	N
REVEL	Benign	0.12
Sift	Benign	0.75	T
Sift4G	Benign	0.70	T
Polyphen		0.0010	B
Vest4		0.050
MutPred		0.35		Gain of disorder (P = 0.0534);
MVP		0.82
MPC		0.14
ClinPred		0.027	T
GERP RS		-2.6
Varity_R		0.028
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr2-105705524;