chr17-81704245-C-T

Variant summary

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

The NM_002949.4(MRPL12):​c.76C>T​(p.Arg26*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,014 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. Synonymous variant affecting the same amino acid position (i.e. R26R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MRPL12
NM_002949.4 stop_gained, splice_region

Scores

2
3
2
Splicing: ADA: 0.9870
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.93

Publications

0 publications found
Variant links:
Genes affected
MRPL12 (HGNC:10378): (mitochondrial ribosomal protein L12) 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 39S subunit protein which forms homodimers. In prokaryotic ribosomes, two L7/L12 dimers and one L10 protein form the L8 protein complex. [provided by RefSeq, Jul 2008]
MRPL12 Gene-Disease associations (from GenCC):
  • combined oxidative phosphorylation deficiency 45
    Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL12NM_002949.4 linkc.76C>T p.Arg26* stop_gained, splice_region_variant Exon 2 of 5 ENST00000333676.8 NP_002940.2 P52815

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL12ENST00000333676.8 linkc.76C>T p.Arg26* stop_gained, splice_region_variant Exon 2 of 5 1 NM_002949.4 ENSP00000333837.3 P52815
ENSG00000262660ENST00000571730.1 linkc.76C>T p.Arg26* stop_gained, splice_region_variant Exon 2 of 15 2 ENSP00000461324.1 B4DLN1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000414
AC:
1
AN:
241806
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1452014
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
722046
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33170
American (AMR)
AF:
0.00
AC:
0
AN:
43348
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25642
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39592
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85270
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52724
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4340
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1108048
Other (OTH)
AF:
0.00
AC:
0
AN:
59880
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.50
D
BayesDel_noAF
Pathogenic
0.59
CADD
Pathogenic
42
DANN
Uncertain
1.0
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Benign
0.76
D
PhyloP100
2.9
Vest4
0.14
GERP RS
5.1
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.1
Mutation Taster
=31/169
disease causing (fs/PTC)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.99
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1214696093; hg19: chr17-79671275; API