Variant 20-10412497-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

MKKS (HGNC:):

MKKS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 261060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-10412497-C-G is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MKKS	NM_170784.3 linkuse as main transcript	c.985+33G>C	intron_variant	ENST00000347364.7	NP_740754.1	Q9NPJ1B7Z3W9
MKKS	NM_018848.3 linkuse as main transcript	c.985+33G>C	intron_variant		NP_061336.1	Q9NPJ1B7Z3W9
MKKS	NR_072977.2 linkuse as main transcript	n.347-3694G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MKKS	ENST00000347364.7 linkuse as main transcript	c.985+33G>C	intron_variant	1	NM_170784.3	ENSP00000246062.4	Q9NPJ1
MKKS	ENST00000399054.6 linkuse as main transcript	c.985+33G>C	intron_variant	1		ENSP00000382008.2	Q9NPJ1
MKKS	ENST00000651692.1 linkuse as main transcript	c.985+33G>C	intron_variant			ENSP00000498849.1	Q9NPJ1
MKKS	ENST00000652676.1 linkuse as main transcript	n.629+33G>C	intron_variant

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

GnomAD3 exomes

AF:

0.254

AC:

62817

AN:

247060

Hom.:

8728

AF XY:

0.246

AC XY:

32989

AN XY:

134080

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 SAS exome

AF:

0.215

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

Gnomad4 AFR exome

AF:

0.310

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.220

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.255

AC:

38820

AN:

152086

Hom.:

5121

Cov.:

AF XY:

0.255

AC XY:

18942

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.269

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.6

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over