Variant chr20-10408832-T-A 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.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:3

Conservation

PhyloP100: 0.346

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:

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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=-0.77).

BP6

Variant 20-10408832-T-A is Benign according to our data. Variant chr20-10408832-T-A is described in ClinVar as [Benign]. Clinvar id is 261061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-10408832-T-A is described in Lovd as [Likely_pathogenic]. Variant chr20-10408832-T-A is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MKKS	NM_170784.3 linkuse as main transcript	c.986-29A>T	intron_variant	ENST00000347364.7
MKKS	NM_018848.3 linkuse as main transcript	c.986-29A>T	intron_variant
MKKS	NR_072977.2 linkuse as main transcript	n.347-29A>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
MKKS	ENST00000347364.7 linkuse as main transcript	c.986-29A>T	intron_variant	1	NM_170784.3	P1
MKKS	ENST00000399054.6 linkuse as main transcript	c.986-29A>T	intron_variant	1		P1
MKKS	ENST00000651692.1 linkuse as main transcript	c.986-29A>T	intron_variant			P1
MKKS	ENST00000652676.1 linkuse as main transcript	n.630-29A>T	intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.152

AC:

36553

AN:

239872

Hom.:

3459

AF XY:

0.153

AC XY:

19881

AN XY:

129968

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 SAS exome

AF:

0.249

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

Gnomad4 AFR exome

AF:

0.340

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.245

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.185

AC:

28155

AN:

152126

Hom.:

3387

Cov.:

AF XY:

0.190

AC XY:

14103

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.164

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

McKusick-Kaufman syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.5

DANN

Benign

0.55

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

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