rs137853154
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_170784.3(MKKS):c.442C>T(p.Gln148Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,700 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MKKS
NM_170784.3 stop_gained
NM_170784.3 stop_gained
Scores
1
3
3
Clinical Significance
Conservation
PhyloP100: 1.66
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 11 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 20-10413073-G-A is Pathogenic according to our data. Variant chr20-10413073-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 5318.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MKKS | NM_170784.3 | c.442C>T | p.Gln148Ter | stop_gained | 3/6 | ENST00000347364.7 | |
MKKS | NM_018848.3 | c.442C>T | p.Gln148Ter | stop_gained | 3/6 | ||
MKKS | NR_072977.2 | n.347-4270C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MKKS | ENST00000347364.7 | c.442C>T | p.Gln148Ter | stop_gained | 3/6 | 1 | NM_170784.3 | P1 | |
MKKS | ENST00000399054.6 | c.442C>T | p.Gln148Ter | stop_gained | 3/6 | 1 | P1 | ||
MKKS | ENST00000651692.1 | c.442C>T | p.Gln148Ter | stop_gained | 4/7 | P1 | |||
MKKS | ENST00000652676.1 | n.459-373C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461700Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727168
GnomAD4 exome
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34
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2
AN XY:
727168
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Bardet-biedl syndrome 2/6, digenic Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 21, 2001 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A
Vest4
GERP RS
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