rs6133917

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018848.3(MKKS):c.985+16T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,611,466 control chromosomes in the GnomAD database, including 14,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1778 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12573 hom. )

Consequence

MKKS
NM_018848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0780

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 20-10412514-A-C is Benign according to our data. Variant chr20-10412514-A-C is described in ClinVar as Benign. ClinVar VariationId is 196492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018848.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MKKS	NM_170784.3	MANE Select	c.985+16T>G	intron	N/A	NP_740754.1
MKKS	NM_018848.3		c.985+16T>G	intron	N/A	NP_061336.1
MKKS	NR_072977.2		n.347-3711T>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MKKS	ENST00000347364.7	TSL:1 MANE Select	c.985+16T>G	intron	N/A	ENSP00000246062.4
MKKS	ENST00000399054.6	TSL:1	c.985+16T>G	intron	N/A	ENSP00000382008.2
MKKS	ENST00000651692.1		c.985+16T>G	intron	N/A	ENSP00000498849.1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21919

AN:

152096

Hom.:

1773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

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

GnomAD2 exomes

AF:

0.140

AC:

35060

AN:

249660

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.0999

Gnomad EAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.124

AC:

181139

AN:

1459252

Hom.:

12573

Cov.:

AF XY:

0.127

AC XY:

92124

AN XY:

726090

show subpopulations

African (AFR)

AF:

0.195

AC:

6509

AN:

33444

American (AMR)

AF:

0.109

AC:

4866

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

2652

AN:

26130

East Asian (EAS)

AF:

0.245

AC:

9707

AN:

39682

South Asian (SAS)

AF:

0.240

AC:

20718

AN:

86204

European-Finnish (FIN)

AF:

0.116

AC:

5995

AN:

51898

Middle Eastern (MID)

AF:

0.135

AC:

778

AN:

5762

European-Non Finnish (NFE)

AF:

0.110

AC:

121840

AN:

1111062

Other (OTH)

AF:

0.134

AC:

8074

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

7574

15148

22722

30296

37870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4678

9356

14034

18712

23390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.144

AC:

21946

AN:

152214

Hom.:

1778

Cov.:

AF XY:

0.150

AC XY:

11156

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.193

AC:

7998

AN:

41528

American (AMR)

AF:

0.151

AC:

2302

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

364

AN:

3470

East Asian (EAS)

AF:

0.242

AC:

1253

AN:

5178

South Asian (SAS)

AF:

0.235

AC:

1136

AN:

4826

European-Finnish (FIN)

AF:

0.118

AC:

1255

AN:

10604

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.107

AC:

7304

AN:

67998

Other (OTH)

AF:

0.133

AC:

280

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

946

1891

2837

3782

4728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.103

Hom.:

395

Bravo

AF:

0.144

Asia WGS

AF:

0.214

AC:

744

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Bardet-Biedl syndrome;C0948368:McKusick-Kaufman syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.5

(source)

DANN

Benign

0.86

PhyloP100

-0.078

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over