Variant chr17-58212973-T-C 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.858+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,612,244 control chromosomes in the GnomAD database, including 168,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23281 hom., cov: 31)

Exomes 𝑓: 0.44 ( 145645 hom. )

Consequence

MKS1
NM_017777.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.77

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:

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=-0.92).

BP6

Variant 17-58212973-T-C is Benign according to our data. Variant chr17-58212973-T-C is described in ClinVar as [Benign]. Clinvar id is 126274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-58212973-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKS1	NM_017777.4 link	c.858+9A>G		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 link	c.858+9A>G		intron_variant		1	NM_017777.4	ENSP00000376827.2		Q9NXB0-1

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79717

AN:

151828

Hom.:

23227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.491

GnomAD3 exomes

AF:

0.434

AC:

108173

AN:

249504

Hom.:

25673

AF XY:

0.434

AC XY:

58700

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.803

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.208

Gnomad SAS exome

AF:

0.439

Gnomad FIN exome

AF:

0.526

Gnomad NFE exome

AF:

0.446

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.438

AC:

640240

AN:

1460298

Hom.:

145645

Cov.:

AF XY:

0.438

AC XY:

318073

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.812

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.457

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.445

Gnomad4 FIN exome

AF:

0.519

Gnomad4 NFE exome

AF:

0.437

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.525

AC:

79832

AN:

151946

Hom.:

23281

Cov.:

AF XY:

0.522

AC XY:

38786

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.792

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.458

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.429

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.443

Gnomad4 OTH

AF:

0.489

Alfa

AF:

0.450

Hom.:

25898

Bravo

AF:

0.523

Asia WGS

AF:

0.344

AC:

1197

AN:

3478

EpiCase

AF:

0.427

EpiControl

AF:

0.429

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Meckel syndrome, type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Bardet-Biedl syndrome 13

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

-0.92

CADD

Benign

0.031

DANN

Benign

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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