rs16991547
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_170784.3(MKKS):c.117C>T(p.Pro39Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,612,488 control chromosomes in the GnomAD database, including 17,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_170784.3 synonymous
Scores
Clinical Significance
Conservation
Publications
- McKusick-Kaufman syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
- Bardet-Biedl syndrome 6Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- Bardet-Biedl syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MKKS | NM_170784.3 | c.117C>T | p.Pro39Pro | synonymous_variant | Exon 3 of 6 | ENST00000347364.7 | NP_740754.1 | |
MKKS | NM_018848.3 | c.117C>T | p.Pro39Pro | synonymous_variant | Exon 3 of 6 | NP_061336.1 | ||
MKKS | NR_072977.2 | n.347-4595C>T | intron_variant | Intron 2 of 4 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.184 AC: 28018AN: 151952Hom.: 3357 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.151 AC: 38009AN: 251064 AF XY: 0.152 show subpopulations
GnomAD4 exome AF: 0.129 AC: 187710AN: 1460422Hom.: 14117 Cov.: 34 AF XY: 0.131 AC XY: 94882AN XY: 726186 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.184 AC: 28055AN: 152066Hom.: 3364 Cov.: 32 AF XY: 0.189 AC XY: 14064AN XY: 74360 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Benign:5
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Benign:2
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Bardet-Biedl syndrome;C0948368:McKusick-Kaufman syndrome Benign:1
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McKusick-Kaufman syndrome Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Bardet-Biedl syndrome 6 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Bardet-Biedl syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at