chr13-23760186-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBS1_Supporting
The NM_005932.4(MIPEP):c.1880G>A(p.Gly627Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G627G) has been classified as Likely benign.
Frequency
Consequence
NM_005932.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MIPEP | NM_005932.4 | c.1880G>A | p.Gly627Glu | missense_variant | 17/19 | ENST00000382172.4 | |
MIPEP | XM_011535097.3 | c.1694G>A | p.Gly565Glu | missense_variant | 17/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MIPEP | ENST00000382172.4 | c.1880G>A | p.Gly627Glu | missense_variant | 17/19 | 1 | NM_005932.4 | P1 | |
MIPEP | ENST00000433710.2 | n.73G>A | non_coding_transcript_exon_variant | 2/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251312Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135824
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461826Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727208
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74374
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2023 | The c.1880G>A (p.G627E) alteration is located in exon 17 (coding exon 17) of the MIPEP gene. This alteration results from a G to A substitution at nucleotide position 1880, causing the glycine (G) at amino acid position 627 to be replaced by a glutamic acid (E). 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 | Aug 30, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MIPEP protein function. ClinVar contains an entry for this variant (Variation ID: 2180652). This variant has not been reported in the literature in individuals affected with MIPEP-related conditions. This variant is present in population databases (rs183315697, gnomAD 0.005%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 627 of the MIPEP protein (p.Gly627Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at