2-105089047-C-T

Position:

• chr2-105089047-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182640.3(MRPS9):​c.553C>T​(p.Leu185Phe) 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. 15/21 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: MRPS9 NM_182640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.131

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057635874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS9	NM_182640.3	c.553C>T	p.Leu185Phe	missense_variant	6/11	ENST00000258455.8	NP_872578.1
MRPS9	XM_011511644.3	c.181C>T	p.Leu61Phe	missense_variant	5/10		XP_011509946.1
MRPS9	XM_047445533.1	c.553C>T	p.Leu185Phe	missense_variant	6/7		XP_047301489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS9	ENST00000258455.8	c.553C>T	p.Leu185Phe	missense_variant	6/11	1	NM_182640.3	ENSP00000258455	P1
MRPS9	ENST00000413583.5	c.31C>T	p.Leu11Phe	missense_variant, NMD_transcript_variant	1/6	3		ENSP00000388885

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

MRPS9: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	0.35
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.70	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.13
Sift	Benign	0.77	T
Sift4G	Benign	0.75	T
Polyphen		0.0010	B
Vest4		0.054
MutPred		0.29		Gain of methylation at K188 (P = 0.081);
MVP		0.88
MPC		0.17
ClinPred		0.090	T
GERP RS		2.5
Varity_R		0.030
gMVP		0.40

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: chr2-105705505;