chr15-89750733-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_018670.4(MESP1):c.499C>G(p.Pro167Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000674 in 1,424,928 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P167T) has been classified as Uncertain significance.
Frequency
Consequence
NM_018670.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MESP1 | NM_018670.4 | c.499C>G | p.Pro167Ala | missense_variant | 1/2 | ENST00000300057.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MESP1 | ENST00000300057.5 | c.499C>G | p.Pro167Ala | missense_variant | 1/2 | 1 | NM_018670.4 | P1 | |
MESP1 | ENST00000559894.1 | n.114+291C>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152196Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.0000668 AC: 85AN: 1272732Hom.: 0 Cov.: 65 AF XY: 0.0000611 AC XY: 38AN XY: 622332
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152196Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2024 | The c.499C>G (p.P167A) alteration is located in exon 1 (coding exon 1) of the MESP1 gene. This alteration results from a C to G substitution at nucleotide position 499, causing the proline (P) at amino acid position 167 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 167 of the MESP1 protein (p.Pro167Ala). This variant is present in population databases (rs767947453, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with MESP1-related conditions. 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. 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