rs16991547

Positions:

chr20-10413398-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_170784.3(MKKS):c.117C>T(p.Pro39=) 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

Genomes: 𝑓 0.18 ( 3364 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14117 hom. )

Consequence

MKKS
NM_170784.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.15

Variant links:

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]

MKKS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 20-10413398-G-A is Benign according to our data. Variant chr20-10413398-G-A is described in ClinVar as [Benign]. Clinvar id is 21669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-10413398-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MKKS	NM_170784.3 linkuse as main transcript	c.117C>T	p.Pro39=	synonymous_variant	3/6	ENST00000347364.7
MKKS	NM_018848.3 linkuse as main transcript	c.117C>T	p.Pro39=	synonymous_variant	3/6
MKKS	NR_072977.2 linkuse as main transcript	n.347-4595C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MKKS	ENST00000347364.7 linkuse as main transcript	c.117C>T	p.Pro39=	synonymous_variant	3/6	1	NM_170784.3	P1
MKKS	ENST00000399054.6 linkuse as main transcript	c.117C>T	p.Pro39=	synonymous_variant	3/6	1		P1
MKKS	ENST00000651692.1 linkuse as main transcript	c.117C>T	p.Pro39=	synonymous_variant	4/7			P1
MKKS	ENST00000652676.1 linkuse as main transcript	n.458+398C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

28018

AN:

151952

Hom.:

3357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.165

GnomAD3 exomes

AF:

0.151

AC:

38009

AN:

251064

Hom.:

3631

AF XY:

0.152

AC XY:

20582

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.235

Gnomad SAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.129

AC:

187710

AN:

1460422

Hom.:

14117

Cov.:

AF XY:

0.131

AC XY:

94882

AN XY:

726186

show subpopulations

Gnomad4 AFR exome

AF:

0.337

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.184

AC:

28055

AN:

152066

Hom.:

3364

Cov.:

AF XY:

0.189

AC XY:

14064

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.125

Hom.:

2328

Bravo

AF:

0.191

Asia WGS

AF:

0.221

AC:

766

AN:

3478

EpiCase

AF:

0.110

EpiControl

AF:

0.110

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 06, 2015	- -

Bardet-Biedl syndrome;C0948368:McKusick-Kaufman syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

McKusick-Kaufman syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

not provided

Benign:1

Likely benign, no assertion criteria provided

literature only

Department of Ophthalmology and Visual Sciences Kyoto University

- -

Bardet-Biedl syndrome 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Bardet-Biedl syndrome

Benign:1

Benign, no assertion criteria provided

curation

GeneReviews

Oct 13, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.84

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over