Variant 17-58206088-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_001321269.2(MKS1):c.1588G>C(p.Gly530Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,611,270 control chromosomes in the GnomAD database, including 1,584 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 559 hom., cov: 32)

Exomes 𝑓: 0.030 ( 1025 hom. )

Consequence

MKS1
NM_001321269.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.318

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=-0.8).

BP6

Variant 17-58206088-C-G is Benign according to our data. Variant chr17-58206088-C-G is described in ClinVar as [Benign]. Clinvar id is 126272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-58206088-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 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.1671G>C	p.Leu557Leu	synonymous_variant	18/18	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.1671G>C	p.Leu557Leu	synonymous_variant	18/18	1	NM_017777.4	ENSP00000376827.2		Q9NXB0-1

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9638

AN:

152080

Hom.:

557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0363

Gnomad ASJ

AF:

0.0671

Gnomad EAS

AF:

0.00791

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.0296

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0657

GnomAD3 exomes

AF:

0.0369

AC:

8919

AN:

241980

Hom.:

270

AF XY:

0.0353

AC XY:

4657

AN XY:

131758

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.0263

Gnomad ASJ exome

AF:

0.0718

Gnomad EAS exome

AF:

0.00635

Gnomad SAS exome

AF:

0.0290

Gnomad FIN exome

AF:

0.0276

Gnomad NFE exome

AF:

0.0293

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0304

AC:

44418

AN:

1459072

Hom.:

1025

Cov.:

AF XY:

0.0303

AC XY:

21959

AN XY:

725694

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.0289

Gnomad4 ASJ exome

AF:

0.0699

Gnomad4 EAS exome

AF:

0.0128

Gnomad4 SAS exome

AF:

0.0291

Gnomad4 FIN exome

AF:

0.0303

Gnomad4 NFE exome

AF:

0.0258

Gnomad4 OTH exome

AF:

0.0391

GnomAD4 genome

AF:

0.0634

AC:

9645

AN:

152198

Hom.:

559

Cov.:

AF XY:

0.0626

AC XY:

4655

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.0363

Gnomad4 ASJ

AF:

0.0671

Gnomad4 EAS

AF:

0.00793

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.0296

Gnomad4 NFE

AF:

0.0277

Gnomad4 OTH

AF:

0.0650

Alfa

AF:

0.0253

Hom.:

Bravo

AF:

0.0686

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 20, 2013	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. -
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	-	- -

Meckel syndrome, type 1

Benign:3

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, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 08, 2021	- -
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	Jul 08, 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. -

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.81

DANN

Benign

0.59

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