rs764266

Variant names:

Variant summary

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

The NM_170784.3(MKKS):c.986-29A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,565,076 control chromosomes in the GnomAD database, including 17,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3387 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13816 hom. )

Consequence

MKKS
NM_170784.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.346

Publications

7 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=-0.77).

BP6

Variant 20-10408832-T-A is Benign according to our data. Variant chr20-10408832-T-A is described in ClinVar as Benign. ClinVar VariationId is 261061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MKKS	NM_170784.3 link	c.986-29A>T	intron_variant	Intron 3 of 5	ENST00000347364.7	NP_740754.1	Q9NPJ1B7Z3W9
MKKS	NM_018848.3 link	c.986-29A>T	intron_variant	Intron 3 of 5		NP_061336.1	Q9NPJ1B7Z3W9
MKKS	NR_072977.2 link	n.347-29A>T	intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MKKS	ENST00000347364.7 link	c.986-29A>T	intron_variant	Intron 3 of 5	1	NM_170784.3	ENSP00000246062.4	Q9NPJ1
MKKS	ENST00000399054.6 link	c.986-29A>T	intron_variant	Intron 3 of 5	1		ENSP00000382008.2	Q9NPJ1
MKKS	ENST00000651692.1 link	c.986-29A>T	intron_variant	Intron 4 of 6			ENSP00000498849.1	Q9NPJ1
MKKS	ENST00000652676.1 link	n.630-29A>T	intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28116

AN:

152006

Hom.:

3380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.0253

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.166

GnomAD2 exomes

AF:

0.152

AC:

36553

AN:

239872

AF XY:

0.153

show subpopulations

Gnomad AFR exome

AF:

0.340

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.130

AC:

183011

AN:

1412950

Hom.:

13816

Cov.:

AF XY:

0.132

AC XY:

92789

AN XY:

705022

show subpopulations

African (AFR)

AF:

0.340

AC:

11078

AN:

32536

American (AMR)

AF:

0.119

AC:

5257

AN:

44254

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2638

AN:

25642

East Asian (EAS)

AF:

0.245

AC:

9664

AN:

39440

South Asian (SAS)

AF:

0.241

AC:

20359

AN:

84436

European-Finnish (FIN)

AF:

0.116

AC:

6056

AN:

52116

Middle Eastern (MID)

AF:

0.146

AC:

687

AN:

4710

European-Non Finnish (NFE)

AF:

0.111

AC:

118872

AN:

1071220

Other (OTH)

AF:

0.143

AC:

8400

AN:

58596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

7759

15518

23277

31036

38795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4608

9216

13824

18432

23040

<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:

0.185

AC:

28155

AN:

152126

Hom.:

3387

Cov.:

AF XY:

0.190

AC XY:

14103

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.332

AC:

13792

AN:

41482

American (AMR)

AF:

0.170

AC:

2597

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

370

AN:

3466

East Asian (EAS)

AF:

0.243

AC:

1255

AN:

5172

South Asian (SAS)

AF:

0.237

AC:

1144

AN:

4826

European-Finnish (FIN)

AF:

0.119

AC:

1257

AN:

10604

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7337

AN:

67992

Other (OTH)

AF:

0.164

AC:

346

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1109

2218

3328

4437

5546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.141

Hom.:

359

Bravo

AF:

0.191

Asia WGS

AF:

0.220

AC:

762

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 17, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

McKusick-Kaufman syndrome

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.5

(source)

DANN

Benign

0.55

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(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

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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