20-10413588-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_170784.3(MKKS):c.-74G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,486,048 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

MKKS
NM_170784.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.500

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

McKusick-Kaufman syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
Bardet-Biedl syndrome 6
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MKKS links:

ENSG00000285508 (HGNC:):

ENSG00000285508 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 20-10413588-C-T is Benign according to our data. Variant chr20-10413588-C-T is described in ClinVar as [Benign]. Clinvar id is 21668.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKKS	NM_170784.3 link	c.-74G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 6	ENST00000347364.7	NP_740754.1	Q9NPJ1B7Z3W9
MKKS	NM_170784.3 link	c.-74G>A		5_prime_UTR_variant	Exon 3 of 6	ENST00000347364.7	NP_740754.1	Q9NPJ1B7Z3W9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MKKS	ENST00000347364.7 link	c.-74G>A	5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 6	1	NM_170784.3	ENSP00000246062.4	Q9NPJ1
MKKS	ENST00000347364.7 link	c.-74G>A	5_prime_UTR_variant	Exon 3 of 6	1	NM_170784.3	ENSP00000246062.4	Q9NPJ1
ENSG00000285723	ENST00000649912.2 link	c.*362G>A	downstream_gene_variant				ENSP00000497510.1	Q9HB66
ENSG00000285508	ENST00000713549.1 link	c.*147G>A	downstream_gene_variant				ENSP00000518845.1

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000957

GnomAD4 exome

AF:

0.000159

AC:

212

AN:

1333804

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

102

AN XY:

670348

show subpopulations

African (AFR)

AF:

0.00259

AC:

AN:

30492

American (AMR)

AF:

0.000343

AC:

AN:

43712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25224

East Asian (EAS)

AF:

0.000205

AC:

AN:

39052

South Asian (SAS)

AF:

0.000290

AC:

AN:

82768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50644

Middle Eastern (MID)

AF:

0.000887

AC:

AN:

4512

European-Non Finnish (NFE)

AF:

0.0000569

AC:

AN:

1001366

Other (OTH)

AF:

0.000446

AC:

AN:

56034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152244

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00260

AC:

108

AN:

41534

American (AMR)

AF:

0.000458

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68022

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000555

Hom.:

Bravo

AF:

0.00112

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome

Benign:1

Oct 13, 2009

GeneReviews

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.4

(source)

DANN

Benign

0.53

PhyloP100

0.50

Mutation Taster

=299/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

20-10413588-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over