rs2294901

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_170784.3(MKKS):c.*392T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 162,214 control chromosomes in the GnomAD database, including 1,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1781 hom., cov: 32)

Exomes 𝑓: 0.12 ( 85 hom. )

Consequence

MKKS
NM_170784.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.346

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-10404855-A-G is Benign according to our data. Variant chr20-10404855-A-G is described in ClinVar as [Benign]. Clinvar id is 337686.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MKKS	NM_170784.3 linkuse as main transcript	c.*392T>C	3_prime_UTR_variant	6/6	ENST00000347364.7
MKKS	NM_018848.3 linkuse as main transcript	c.*392T>C	3_prime_UTR_variant	6/6
MKKS	NR_072977.2 linkuse as main transcript	n.1466T>C	non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKKS	ENST00000347364.7 linkuse as main transcript	c.*392T>C		3_prime_UTR_variant	6/6	1	NM_170784.3	P1
MKKS	ENST00000651692.1 linkuse as main transcript	c.*392T>C		3_prime_UTR_variant	7/7			P1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21967

AN:

152050

Hom.:

1776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.119

AC:

1199

AN:

10046

Hom.:

Cov.:

AF XY:

0.128

AC XY:

693

AN XY:

5420

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.0820

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0965

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.145

AC:

21996

AN:

152168

Hom.:

1781

Cov.:

AF XY:

0.150

AC XY:

11184

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.235

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.127

Hom.:

172

Bravo

AF:

0.145

Asia WGS

AF:

0.213

AC:

741

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

McKusick-Kaufman syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Bardet-Biedl syndrome 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

2.0

Dann

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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