dbSNP rs758278030: MRPS12:p.Pro42Thr (chr19-38932407-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033362.4(MRPS12):c.124C>A(p.Pro42Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MRPS12
NM_033362.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.88

Variant links:

Genes affected

MRPS12 (HGNC:10380): (mitochondrial ribosomal protein S12) 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 S12P family. The encoded protein is a key component of the ribosomal small subunit and controls the decoding fidelity and susceptibility to aminoglycoside antibiotics. The gene for mitochondrial seryl-tRNA synthetase is located upstream and adjacent to this gene, and both genes are possible candidates for the autosomal dominant deafness gene (DFNA4). Splice variants that differ in the 5' UTR have been found for this gene; all three variants encode the same protein. [provided by RefSeq, Jul 2008]

MRPS12 links:

ENSG00000269547 (HGNC:):

ENSG00000269547 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3589905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS12	NM_033362.4 link	c.124C>A	p.Pro42Thr	missense_variant	Exon 3 of 3	ENST00000308018.9	NP_203526.1	O15235A0A024R0H2
MRPS12	NM_021107.1 link	c.124C>A	p.Pro42Thr	missense_variant	Exon 2 of 2		NP_066930.1	O15235A0A024R0H2
MRPS12	NM_033363.1 link	c.124C>A	p.Pro42Thr	missense_variant	Exon 3 of 3		NP_203527.1	O15235A0A024R0H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRPS12	ENST00000308018.9 link	c.124C>A	p.Pro42Thr	missense_variant	Exon 3 of 3	1	NM_033362.4	ENSP00000308845.3	O15235
MRPS12	ENST00000402029.3 link	c.124C>A	p.Pro42Thr	missense_variant	Exon 3 of 3	1		ENSP00000384579.2	O15235
MRPS12	ENST00000407800.2 link	c.124C>A	p.Pro42Thr	missense_variant	Exon 2 of 2	1		ENSP00000384952.1	O15235
ENSG00000269547	ENST00000599996.1 link	c.475-6107G>T		intron_variant	Intron 5 of 19	2		ENSP00000472465.1	M0R2C6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.040

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.019

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;L;L

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.19

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.43

MutPred

0.38

Loss of catalytic residue at P41 (P = 0.0131);Loss of catalytic residue at P41 (P = 0.0131);Loss of catalytic residue at P41 (P = 0.0131);

MVP

0.58

MPC

1.2

ClinPred

0.86

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over