rs764266
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_170784.3(MKKS):c.986-29A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,565,076 control chromosomes in the GnomAD database, including 17,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.19 ( 3387 hom., cov: 32)
Exomes 𝑓: 0.13 ( 13816 hom. )
Consequence
MKKS
NM_170784.3 intron
NM_170784.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.346
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 Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MKKS | NM_170784.3 | c.986-29A>T | intron_variant | ENST00000347364.7 | |||
MKKS | NM_018848.3 | c.986-29A>T | intron_variant | ||||
MKKS | NR_072977.2 | n.347-29A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MKKS | ENST00000347364.7 | c.986-29A>T | intron_variant | 1 | NM_170784.3 | P1 | |||
MKKS | ENST00000399054.6 | c.986-29A>T | intron_variant | 1 | P1 | ||||
MKKS | ENST00000651692.1 | c.986-29A>T | intron_variant | P1 | |||||
MKKS | ENST00000652676.1 | n.630-29A>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.185 AC: 28116AN: 152006Hom.: 3380 Cov.: 32
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GnomAD3 exomes AF: 0.152 AC: 36553AN: 239872Hom.: 3459 AF XY: 0.153 AC XY: 19881AN XY: 129968
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GnomAD4 exome AF: 0.130 AC: 183011AN: 1412950Hom.: 13816 Cov.: 26 AF XY: 0.132 AC XY: 92789AN XY: 705022
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GnomAD4 genome ? AF: 0.185 AC: 28155AN: 152126Hom.: 3387 Cov.: 32 AF XY: 0.190 AC XY: 14103AN XY: 74384
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
McKusick-Kaufman syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 17, 2019 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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