22-19432581-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001318151.2(MRPL40):c.-358C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,553,496 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 (★).
Frequency
Consequence
NM_001318151.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRPL40 | NM_003776.4 | c.27C>G | p.Ile9Met | missense_variant | Exon 1 of 4 | ENST00000333130.4 | NP_003767.2 | |
MRPL40 | NM_001318151.2 | c.-358C>G | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 4 | NP_001305080.1 | |||
MRPL40 | NM_001318151.2 | c.-358C>G | 5_prime_UTR_variant | Exon 1 of 4 | NP_001305080.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MRPL40 | ENST00000333130.4 | c.27C>G | p.Ile9Met | missense_variant | Exon 1 of 4 | 1 | NM_003776.4 | ENSP00000333401.3 | ||
MRPL40 | ENST00000443660.5 | n.3C>G | non_coding_transcript_exon_variant | Exon 1 of 4 | 2 | |||||
HIRA | ENST00000452818.1 | n.72+14797G>C | intron_variant | Intron 1 of 5 | 5 | ENSP00000404792.1 | ||||
C22orf39 | ENST00000509549.5 | n.192+14797G>C | intron_variant | Intron 2 of 23 | 2 | ENSP00000424903.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000452 AC: 7AN: 154808Hom.: 0 AF XY: 0.0000362 AC XY: 3AN XY: 82958
GnomAD4 exome AF: 0.0000164 AC: 23AN: 1401248Hom.: 0 Cov.: 30 AF XY: 0.0000159 AC XY: 11AN XY: 692102
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74388
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant is present in population databases (no rsID available, gnomAD 0.02%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with MRPL40-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 9 of the MRPL40 protein (p.Ile9Met). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at