20-10405256-A-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The ENST00000347364.7(MKKS):āc.1704T>Cā(p.Asp568=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000186 in 1,610,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
MKKS
ENST00000347364.7 synonymous
ENST00000347364.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.81
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 20-10405256-A-G is Benign according to our data. Variant chr20-10405256-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2945991.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MKKS | NM_170784.3 | c.1704T>C | p.Asp568= | synonymous_variant | 6/6 | ENST00000347364.7 | NP_740754.1 | |
MKKS | NM_018848.3 | c.1704T>C | p.Asp568= | synonymous_variant | 6/6 | NP_061336.1 | ||
MKKS | NR_072977.2 | n.1065T>C | non_coding_transcript_exon_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MKKS | ENST00000347364.7 | c.1704T>C | p.Asp568= | synonymous_variant | 6/6 | 1 | NM_170784.3 | ENSP00000246062 | P1 | |
MKKS | ENST00000399054.6 | c.1704T>C | p.Asp568= | synonymous_variant | 6/6 | 1 | ENSP00000382008 | P1 | ||
MKKS | ENST00000651692.1 | c.1704T>C | p.Asp568= | synonymous_variant | 7/7 | ENSP00000498849 | P1 | |||
MKKS | ENST00000652676.1 | n.1348T>C | non_coding_transcript_exon_variant | 7/7 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246954Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133560
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GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457844Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 725138
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74356
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Bardet-Biedl syndrome;C0948368:McKusick-Kaufman syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2023 | - - |
Computational scores
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Name
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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