2-99195620-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000338148.8(MRPL30):ā€‹c.401T>Cā€‹(p.Met134Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M134V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

MRPL30
ENST00000338148.8 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33
Variant links:
Genes affected
MRPL30 (HGNC:14036): (mitochondrial ribosomal protein L30) 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. Alternative splicing results in multiple transcript variants. Pseudogenes corresponding to this gene are found on chromosomes 6p and 12p. Read-through transcription also exists between this gene and the neighboring upstream lipoyltransferase 1 (LIPT1) gene. [provided by RefSeq, Mar 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21808293).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MRPL30NM_145212.4 linkuse as main transcriptc.401T>C p.Met134Thr missense_variant 6/6 ENST00000338148.8 NP_660213.1 Q8TCC3-1
MRPL30NR_028356.2 linkuse as main transcriptn.494T>C non_coding_transcript_exon_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MRPL30ENST00000338148.8 linkuse as main transcriptc.401T>C p.Met134Thr missense_variant 6/61 NM_145212.4 ENSP00000338057.3 Q8TCC3-1
ENSG00000241962ENST00000424491.5 linkuse as main transcriptn.491T>C non_coding_transcript_exon_variant 9/142 ENSP00000390891.1
MRPL30ENST00000409841.1 linkuse as main transcriptn.401T>C non_coding_transcript_exon_variant 5/65 ENSP00000386752.1 Q8TCC3-1
MRPL30ENST00000465432.1 linkuse as main transcriptn.308T>C non_coding_transcript_exon_variant 4/55

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250074
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135214
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000293
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
6.85e-7
AC:
1
AN:
1460698
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726724
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000226
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 01, 2023The c.401T>C (p.M134T) alteration is located in exon 6 (coding exon 5) of the MRPL30 gene. This alteration results from a T to C substitution at nucleotide position 401, causing the methionine (M) at amino acid position 134 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
22
DANN
Benign
0.93
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.048
Eigen_PC
Benign
0.044
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.14
Sift
Benign
0.084
T
Sift4G
Benign
0.23
T
Polyphen
0.017
B
Vest4
0.48
MVP
0.42
MPC
0.089
ClinPred
0.29
T
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.56
gMVP
0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376234419; hg19: chr2-99812083; API