chr20-10408774-T-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_170784.3(MKKS):āc.1015A>Gā(p.Ile339Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 1,613,792 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_170784.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MKKS | NM_170784.3 | c.1015A>G | p.Ile339Val | missense_variant | 4/6 | ENST00000347364.7 | NP_740754.1 | |
MKKS | NM_018848.3 | c.1015A>G | p.Ile339Val | missense_variant | 4/6 | NP_061336.1 | ||
MKKS | NR_072977.2 | n.376A>G | non_coding_transcript_exon_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MKKS | ENST00000347364.7 | c.1015A>G | p.Ile339Val | missense_variant | 4/6 | 1 | NM_170784.3 | ENSP00000246062.4 | ||
MKKS | ENST00000399054.6 | c.1015A>G | p.Ile339Val | missense_variant | 4/6 | 1 | ENSP00000382008.2 | |||
MKKS | ENST00000651692.1 | c.1015A>G | p.Ile339Val | missense_variant | 5/7 | ENSP00000498849.1 | ||||
MKKS | ENST00000652676.1 | n.659A>G | non_coding_transcript_exon_variant | 5/7 |
Frequencies
GnomAD3 genomes AF: 0.00365 AC: 555AN: 152204Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00422 AC: 1059AN: 251086Hom.: 8 AF XY: 0.00453 AC XY: 615AN XY: 135694
GnomAD4 exome AF: 0.00422 AC: 6174AN: 1461470Hom.: 25 Cov.: 32 AF XY: 0.00434 AC XY: 3154AN XY: 727036
GnomAD4 genome AF: 0.00364 AC: 554AN: 152322Hom.: 1 Cov.: 32 AF XY: 0.00363 AC XY: 270AN XY: 74480
ClinVar
Submissions by phenotype
not specified Benign:6
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 17, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 05, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Sep 23, 2015 | - - |
not provided Benign:4Other:1
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 08, 2021 | This variant is associated with the following publications: (PMID: 22025579, 22090721, 29221435, 18094050, 20498079, 12107442, 15770229, 29127258, 29343940, 20177705) - |
not provided, no classification provided | literature only | NEI Ophthalmic Genomics Laboratory, National Institutes of Health | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | MKKS: BP4, BS2 - |
McKusick-Kaufman syndrome Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Uncertain significance, no assertion criteria provided | research | Tolun Lab, Human Genetics Laboratory, Bogazici University | - | - - |
Bardet-Biedl syndrome 6 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Benign, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | May 31, 2018 | This variant is interpreted as a Benign, for Bardet-biedl syndrome 6, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. - |
Bardet-Biedl syndrome;C0948368:McKusick-Kaufman syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at