Variant rs73329636 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_017777.4(MKS1):c.191-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,584,240 control chromosomes in the GnomAD database, including 1,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 556 hom., cov: 32)

Exomes 𝑓: 0.030 ( 1017 hom. )

Consequence

MKS1
NM_017777.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.506

Variant links:

Genes affected

MKS1 (HGNC:7121): (MKS transition zone complex subunit 1) The protein encoded by this gene localizes to the basal body and is required for formation of the primary cilium in ciliated epithelial cells. Mutations in this gene result in Meckel syndrome type 1 and in Bardet-Biedl syndrome type 13. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

MKS1 links:

MKS1 (HGNC:):

MKS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-58216780-C-T is Benign according to our data. Variant chr17-58216780-C-T is described in ClinVar as [Benign]. Clinvar id is 126273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKS1	NM_017777.4 linkuse as main transcript	c.191-44G>A		intron_variant		ENST00000393119.7	NP_060247.2	Q9NXB0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKS1	ENST00000393119.7 linkuse as main transcript	c.191-44G>A		intron_variant		1	NM_017777.4	ENSP00000376827.2		Q9NXB0-1

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

9602

AN:

152130

Hom.:

554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0367

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.00771

Gnomad SAS

AF:

0.0225

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0645

GnomAD3 exomes

AF:

0.0373

AC:

9230

AN:

247654

Hom.:

283

AF XY:

0.0356

AC XY:

4776

AN XY:

134284

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0265

Gnomad ASJ exome

AF:

0.0723

Gnomad EAS exome

AF:

0.00625

Gnomad SAS exome

AF:

0.0292

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.0295

Gnomad OTH exome

AF:

0.0461

GnomAD4 exome

AF:

0.0305

AC:

43607

AN:

1431992

Hom.:

1017

Cov.:

AF XY:

0.0302

AC XY:

21602

AN XY:

714202

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.0291

Gnomad4 ASJ exome

AF:

0.0700

Gnomad4 EAS exome

AF:

0.0128

Gnomad4 SAS exome

AF:

0.0291

Gnomad4 FIN exome

AF:

0.0303

Gnomad4 NFE exome

AF:

0.0257

Gnomad4 OTH exome

AF:

0.0390

GnomAD4 genome

AF:

0.0631

AC:

9609

AN:

152248

Hom.:

556

Cov.:

AF XY:

0.0622

AC XY:

4634

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.0367

Gnomad4 ASJ

AF:

0.0669

Gnomad4 EAS

AF:

0.00772

Gnomad4 SAS

AF:

0.0223

Gnomad4 FIN

AF:

0.0295

Gnomad4 NFE

AF:

0.0277

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0496

Hom.:

Bravo

AF:

0.0685

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Bardet-Biedl syndrome 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Joubert syndrome 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.70

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