rs587776532
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_138701.4(MPLKIP):βc.277delβ(p.Ser93ProfsTer60) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,559,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. S93S) has been classified as Likely benign.
Frequency
Consequence
NM_138701.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPLKIP | NM_138701.4 | c.277del | p.Ser93ProfsTer60 | frameshift_variant | 1/2 | ENST00000306984.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPLKIP | ENST00000306984.8 | c.277del | p.Ser93ProfsTer60 | frameshift_variant | 1/2 | 1 | NM_138701.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000627 AC: 1AN: 159512Hom.: 0 AF XY: 0.0000117 AC XY: 1AN XY: 85494
GnomAD4 exome AF: 0.0000220 AC: 31AN: 1407536Hom.: 0 Cov.: 32 AF XY: 0.0000144 AC XY: 10AN XY: 695088
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 29, 2023 | Frameshift variant predicted to result in protein truncation, as the last 87 amino acids are replaced with 59 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 31589614, 30598092, 16977596, 25606444, 25290684) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1847). This premature translational stop signal has been observed in individuals with trichothiodystrophy (PMID: 16977596, 25290684, 25606444). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs587776532, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Ser93Profs*60) in the MPLKIP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 87 amino acid(s) of the MPLKIP protein. - |
Trichothiodystrophy 4, nonphotosensitive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at