Variant 17-58206004-G-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_017777.4(MKS1):c.*75C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,550,200 control chromosomes in the GnomAD database, including 7,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.083 ( 586 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7241 hom. )

Consequence

MKS1
NM_017777.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0100

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=-0.78).

BP6

Variant 17-58206004-G-A is Benign according to our data. Variant chr17-58206004-G-A is described in ClinVar as [Benign]. Clinvar id is 324157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MKS1	NM_017777.4 linkuse as main transcript	c.*75C>T		3_prime_UTR_variant	18/18	ENST00000393119.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKS1	ENST00000393119.7 linkuse as main transcript	c.*75C>T		3_prime_UTR_variant	18/18	1	NM_017777.4	P1	Q9NXB0-1

Frequencies

GnomAD3 genomes

AF:

0.0833

AC:

12671

AN:

152044

Hom.:

587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0683

Gnomad ASJ

AF:

0.0876

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0963

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0909

GnomAD4 exome

AF:

0.100

AC:

140446

AN:

1398036

Hom.:

7241

Cov.:

AF XY:

0.101

AC XY:

69595

AN XY:

690208

show subpopulations

Gnomad4 AFR exome

AF:

0.0431

Gnomad4 AMR exome

AF:

0.0535

Gnomad4 ASJ exome

AF:

0.0810

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0958

GnomAD4 genome

AF:

0.0833

AC:

12672

AN:

152164

Hom.:

586

Cov.:

AF XY:

0.0849

AC XY:

6314

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0429

Gnomad4 AMR

AF:

0.0682

Gnomad4 ASJ

AF:

0.0876

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0963

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.0904

Alfa

AF:

0.0573

Hom.:

Bravo

AF:

0.0789

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Meckel syndrome, type 1

Benign:1

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. -

Bardet-Biedl syndrome 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

MKS1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

Cadd

Benign

5.2

Dann

Benign

0.77

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