chr21-25592891-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017446.4(MRPL39):c.842C>T(p.Ser281Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MRPL39
NM_017446.4 missense
NM_017446.4 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 6.52
Genes affected
MRPL39 (HGNC:14027): (mitochondrial ribosomal protein L39) 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. Two transcript variants encoding distinct isoforms have been described. A pseudogene corresponding to this gene is found on chromosome 5q. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPL39 | NM_017446.4 | c.842C>T | p.Ser281Leu | missense_variant | 8/10 | ENST00000352957.9 | |
MRPL39 | NM_080794.4 | c.842C>T | p.Ser281Leu | missense_variant | 8/11 | ||
MRPL39 | XM_006724026.5 | c.842C>T | p.Ser281Leu | missense_variant | 8/10 | ||
MRPL39 | XM_011529651.3 | c.716C>T | p.Ser239Leu | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPL39 | ENST00000352957.9 | c.842C>T | p.Ser281Leu | missense_variant | 8/10 | 1 | NM_017446.4 | P1 | |
MRPL39 | ENST00000307301.11 | c.842C>T | p.Ser281Leu | missense_variant | 8/11 | 5 | |||
MRPL39 | ENST00000419219.1 | c.812C>T | p.Ser271Leu | missense_variant | 8/8 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460578Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0AN XY: 726688
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1460578
Hom.:
Cov.:
41
AF XY:
AC XY:
0
AN XY:
726688
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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 submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.842C>T (p.S281L) alteration is located in exon 8 (coding exon 8) of the MRPL39 gene. This alteration results from a C to T substitution at nucleotide position 842, causing the serine (S) at amino acid position 281 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Uncertain
D;D;D
Polyphen
B;B;.
Vest4
MutPred
Loss of disorder (P = 0.0503);Loss of disorder (P = 0.0503);.;
MVP
MPC
0.082
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.