rs1555801973
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_170784.3(MKKS):c.845_846insA(p.Leu283AlafsTer4) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
MKKS
NM_170784.3 frameshift
NM_170784.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.64
Genes affected
MKKS (HGNC:7108): (MKKS centrosomal shuttling protein) This gene encodes a protein which shares sequence similarity with other members of the type II chaperonin family. The encoded protein is a centrosome-shuttling protein and plays an important role in cytokinesis. This protein also interacts with other type II chaperonin members to form a complex known as the BBSome, which involves ciliary membrane biogenesis. This protein is encoded by a downstream open reading frame (dORF). Several upstream open reading frames (uORFs) have been identified, which repress the translation of the dORF, and two of which can encode small mitochondrial membrane proteins. Mutations in this gene have been observed in patients with Bardet-Biedl syndrome type 6, also known as McKusick-Kaufman syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2023]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 20-10412669-C-CT is Pathogenic according to our data. Variant chr20-10412669-C-CT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 521251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MKKS | NM_170784.3 | c.845_846insA | p.Leu283AlafsTer4 | frameshift_variant | 3/6 | ENST00000347364.7 | |
MKKS | NM_018848.3 | c.845_846insA | p.Leu283AlafsTer4 | frameshift_variant | 3/6 | ||
MKKS | NR_072977.2 | n.347-3867_347-3866insA | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MKKS | ENST00000347364.7 | c.845_846insA | p.Leu283AlafsTer4 | frameshift_variant | 3/6 | 1 | NM_170784.3 | P1 | |
MKKS | ENST00000399054.6 | c.845_846insA | p.Leu283AlafsTer4 | frameshift_variant | 3/6 | 1 | P1 | ||
MKKS | ENST00000651692.1 | c.845_846insA | p.Leu283AlafsTer4 | frameshift_variant | 4/7 | P1 | |||
MKKS | ENST00000652676.1 | n.489_490insA | non_coding_transcript_exon_variant | 4/7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 2016 | - - |
Bardet-Biedl syndrome 6 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 18, 2023 | - - |
Computational scores
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Calibrated prediction
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at