NM_016034.5:c.413G>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PM5PP3

The NM_016034.5(MRPS2):c.413G>T(p.Arg138Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R138H) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MRPS2
NM_016034.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.63

Publications

0 publications found

Variant links:

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]

MRPS2 Gene-Disease associations (from GenCC):

combined oxidative phosphorylation deficiency 36
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

MRPS2 links:

ENSG00000226706 (HGNC:):

ENSG00000226706 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr9-135503655-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 523225.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.805

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MRPS2	NM_016034.5	MANE Select	c.413G>T	p.Arg138Leu	missense	Exon 4 of 4	NP_057118.1
MRPS2	NM_001371401.1		c.413G>T	p.Arg138Leu	missense	Exon 5 of 5	NP_001358330.1
MRPS2	NR_051967.3		n.585G>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MRPS2	ENST00000241600.10	TSL:1 MANE Select	c.413G>T	p.Arg138Leu	missense	Exon 4 of 4	ENSP00000241600.5
ENSG00000226706	ENST00000415062.1	TSL:1	n.735C>A		non_coding_transcript_exon	Exon 3 of 3
MRPS2	ENST00000371785.5	TSL:3	c.413G>T	p.Arg138Leu	missense	Exon 5 of 5	ENSP00000360850.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.6

PhyloP100

8.6

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.42

Sift

Benign

0.031

Sift4G

Uncertain

0.037

Polyphen

1.0

Vest4

0.71

MutPred

0.49

Loss of MoRF binding (P = 0.0436)

MVP

0.80

MPC

0.86

ClinPred

0.99

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.75

gMVP

0.87

Mutation Taster

=9/91

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over