rs149572684
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_023936.2(MRPS34):c.642G>C(p.Lys214Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000821 in 1,607,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_023936.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MRPS34 | ENST00000397375.7 | c.642G>C | p.Lys214Asn | missense_variant | Exon 3 of 3 | 1 | NM_023936.2 | ENSP00000380531.3 | ||
MRPS34 | ENST00000177742.7 | c.663G>C | p.Lys221Asn | missense_variant | Exon 3 of 3 | 1 | ENSP00000177742.3 | |||
MRPS34 | ENST00000569585.1 | n.373G>C | non_coding_transcript_exon_variant | Exon 2 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152252Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000727 AC: 18AN: 247652Hom.: 0 AF XY: 0.0000893 AC XY: 12AN XY: 134404
GnomAD4 exome AF: 0.0000859 AC: 125AN: 1455518Hom.: 0 Cov.: 32 AF XY: 0.0000815 AC XY: 59AN XY: 723962
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74386
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.642G>C (p.K214N) alteration is located in exon 3 (coding exon 3) of the MRPS34 gene. This alteration results from a G to C substitution at nucleotide position 642, causing the lysine (K) at amino acid position 214 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 221 of the MRPS34 protein (p.Lys221Asn). This variant is present in population databases (rs149572684, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MRPS34-related conditions. ClinVar contains an entry for this variant (Variation ID: 2195037). 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 disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at