2-105038108-G-T

Variant names:

• chr2-105038108-G-T
• rs968669025
• NM_182640.3:c.16G>T

Variant summary

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

The NM_182640.3(MRPS9):​c.16G>T​(p.Val6Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. 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. V6E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRPS9 NM_182640.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• Publications: 0 publications found

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]

MRPS9-AS2 (HGNC:40687): (MRPS9 antisense RNA 2)

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=0.0885517).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182640.3. 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
	MRPS9	NM_182640.3	MANE Select	c.16G>T	p.Val6Leu	missense	Exon 1 of 11	NP_872578.1	P82933
	MRPS9-AS2	NR_110603.1		n.43+346C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS9	ENST00000258455.8	TSL:1 MANE Select	c.16G>T	p.Val6Leu	missense	Exon 1 of 11	ENSP00000258455.3	P82933
	MRPS9	ENST00000886286.1		c.16G>T	p.Val6Leu	missense	Exon 1 of 11	ENSP00000556345.1
	MRPS9	ENST00000925255.1		c.16G>T	p.Val6Leu	missense	Exon 1 of 11	ENSP00000595314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.41
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.042
Sift	Benign	0.12	T
Sift4G	Benign	0.21	T
Polyphen		0.022	B
Vest4		0.27
MutPred		0.30		Loss of MoRF binding (P = 0.1425)
MVP		0.39
MPC		0.16
ClinPred		0.078	T
GERP RS		1.8
PromoterAI		0.018	Neutral
Varity_R		0.058
gMVP		0.29
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

dbSNP: rs968669025; hg19: chr2-105654566;