NM_170784.3:c.985+33G>C

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.985+33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,604,844 control chromosomes in the GnomAD database, including 44,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5121 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39047 hom. )

Consequence

MKKS
NM_170784.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.20

Publications

14 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=-0.59).

BP6

Variant 20-10412497-C-G is Benign according to our data. Variant chr20-10412497-C-G is described in ClinVar as Benign. ClinVar VariationId is 261060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MKKS	NM_170784.3 link	c.985+33G>C	intron_variant	Intron 3 of 5	ENST00000347364.7	NP_740754.1
MKKS	NM_018848.3 link	c.985+33G>C	intron_variant	Intron 3 of 5		NP_061336.1
MKKS	NR_072977.2 link	n.347-3694G>C	intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MKKS	ENST00000347364.7 link	c.985+33G>C	intron_variant	Intron 3 of 5	1	NM_170784.3	ENSP00000246062.4
MKKS	ENST00000399054.6 link	c.985+33G>C	intron_variant	Intron 3 of 5	1		ENSP00000382008.2
MKKS	ENST00000651692.1 link	c.985+33G>C	intron_variant	Intron 4 of 6			ENSP00000498849.1
MKKS	ENST00000652676.1 link	n.629+33G>C	intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38780

AN:

151966

Hom.:

5109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.268

GnomAD2 exomes

AF:

0.254

AC:

62817

AN:

247060

AF XY:

0.246

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.388

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.219

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.227

AC:

330306

AN:

1452758

Hom.:

39047

Cov.:

AF XY:

0.226

AC XY:

163742

AN XY:

723136

show subpopulations

African (AFR)

AF:

0.310

AC:

10345

AN:

33340

American (AMR)

AF:

0.378

AC:

16896

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

6240

AN:

26106

East Asian (EAS)

AF:

0.249

AC:

9881

AN:

39650

South Asian (SAS)

AF:

0.214

AC:

18436

AN:

86092

European-Finnish (FIN)

AF:

0.200

AC:

9903

AN:

49638

Middle Eastern (MID)

AF:

0.234

AC:

1338

AN:

5724

European-Non Finnish (NFE)

AF:

0.220

AC:

243216

AN:

1107366

Other (OTH)

AF:

0.234

AC:

14051

AN:

60132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

13011

26022

39033

52044

65055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8566

17132

25698

34264

42830

<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:

0.255

AC:

38820

AN:

152086

Hom.:

5121

Cov.:

AF XY:

0.255

AC XY:

18942

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.305

AC:

12658

AN:

41470

American (AMR)

AF:

0.303

AC:

4630

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

853

AN:

3472

East Asian (EAS)

AF:

0.268

AC:

1384

AN:

5172

South Asian (SAS)

AF:

0.231

AC:

1115

AN:

4824

European-Finnish (FIN)

AF:

0.203

AC:

2148

AN:

10564

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15210

AN:

67978

Other (OTH)

AF:

0.269

AC:

567

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1511

3022

4533

6044

7555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.170

Hom.:

510

Bravo

AF:

0.267

Asia WGS

AF:

0.301

AC:

1047

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 25, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.59

CADD

Benign

5.6

(source)

DANN

Benign

0.77

PhyloP100

-1.2

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)

0.020

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