Variant chr17-58212356-TGCA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_017777.4(MKS1):c.915+19_915+21delTGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,613,470 control chromosomes in the GnomAD database, including 8,110 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.083 ( 576 hom., cov: 31)

Exomes 𝑓: 0.10 ( 7534 hom. )

Consequence

MKS1
NM_017777.4 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.61

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 -16 ACMG points.

BP6

Variant 17-58212356-TGCA-T is Benign according to our data. Variant chr17-58212356-TGCA-T is described in ClinVar as [Benign]. Clinvar id is 260889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-58212356-TGCA-T is described in Lovd as [Benign].

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	Protein	UniProt
MKS1	NM_017777.4 linkuse as main transcript	c.915+19_915+21delTGC		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.915+19_915+21delTGC		intron_variant		1	NM_017777.4	ENSP00000376827.2		Q9NXB0-1

Frequencies

GnomAD3 genomes

AF:

0.0835

AC:

12704

AN:

152152

Hom.:

577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0437

Gnomad AMI

AF:

0.0890

Gnomad AMR

AF:

0.0685

Gnomad ASJ

AF:

0.0878

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.0957

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0913

GnomAD3 exomes

AF:

0.0922

AC:

23016

AN:

249558

Hom.:

1156

AF XY:

0.0955

AC XY:

12928

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.0424

Gnomad AMR exome

AF:

0.0485

Gnomad ASJ exome

AF:

0.0814

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0960

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.0996

GnomAD4 exome

AF:

0.100

AC:

146230

AN:

1461200

Hom.:

7534

AF XY:

0.101

AC XY:

73140

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.0445

Gnomad4 AMR exome

AF:

0.0505

Gnomad4 ASJ exome

AF:

0.0813

Gnomad4 EAS exome

AF:

0.0989

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0997

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0955

GnomAD4 genome

AF:

0.0834

AC:

12706

AN:

152270

Hom.:

576

Cov.:

AF XY:

0.0850

AC XY:

6332

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0437

Gnomad4 AMR

AF:

0.0684

Gnomad4 ASJ

AF:

0.0878

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0957

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.0908

Alfa

AF:

0.0909

Hom.:

102

Bravo

AF:

0.0792

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, flagged submission	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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