rs150920905

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_170784.3(MKKS):c.16G>A(p.Ala6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 1,614,170 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 3 hom. )

Consequence

MKKS
NM_170784.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.35

Publications

3 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
MKKS-related ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
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:

LOC128706665 (HGNC:0):

LOC128706665 links:

ENSG00000285508 (HGNC:):

ENSG00000285508 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075124204).

BP6

Variant 20-10413499-C-T is Benign according to our data. Variant chr20-10413499-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170784.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MKKS	NM_170784.3	MANE Select	c.16G>A	p.Ala6Thr	missense	Exon 3 of 6	NP_740754.1	Q9NPJ1
MKKS	NM_018848.3		c.16G>A	p.Ala6Thr	missense	Exon 3 of 6	NP_061336.1	Q9NPJ1
MKKS	NR_072977.2		n.347-4696G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MKKS	ENST00000347364.7	TSL:1 MANE Select	c.16G>A	p.Ala6Thr	missense	Exon 3 of 6	ENSP00000246062.4	Q9NPJ1
MKKS	ENST00000399054.6	TSL:1	c.16G>A	p.Ala6Thr	missense	Exon 3 of 6	ENSP00000382008.2	Q9NPJ1
MKKS	ENST00000651692.1		c.16G>A	p.Ala6Thr	missense	Exon 4 of 7	ENSP00000498849.1	Q9NPJ1

Frequencies

GnomAD3 genomes

AF:

0.00472

AC:

718

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00106

AC:

267

AN:

250784

AF XY:

0.000782

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000402

AC:

587

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

234

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0137

AC:

458

AN:

33478

American (AMR)

AF:

0.000939

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1112004

Other (OTH)

AF:

0.00123

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00472

AC:

719

AN:

152310

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

365

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0156

AC:

650

AN:

41572

American (AMR)

AF:

0.00366

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

110

146

183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00140

Hom.:

Bravo

AF:

0.00511

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00135

AC:

164

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Bardet-Biedl syndrome 6 (1)

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

McKusick-Kaufman syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0075

MetaSVM

Uncertain

0.098

MutationAssessor

Uncertain

2.6

PhyloP100

1.3

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.38

Sift

Benign

0.053

Sift4G

Benign

0.079

Polyphen

0.96

Vest4

0.065

MVP

0.88

MPC

0.36

ClinPred

0.027

GERP RS

2.9

Varity_R

0.035

gMVP

0.43

Mutation Taster

=93/7

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

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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