Variant chr17-58206040-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_017777.4(MKS1):c.*38del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000532 in 1,582,762 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 3 hom. )

Consequence

MKS1
NM_017777.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.27

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 -16 ACMG points.

BP6

Variant 17-58206040-AT-A is Benign according to our data. Variant chr17-58206040-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 1187069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00293 (446/152222) while in subpopulation AFR AF= 0.0105 (437/41546). AF 95% confidence interval is 0.0097. There are 4 homozygotes in gnomad4. There are 207 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MKS1	NM_017777.4 linkuse as main transcript	c.*38del		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.*38del		3_prime_UTR_variant	18/18	1	NM_017777.4	P1	Q9NXB0-1

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

447

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000638

AC:

127

AN:

199158

Hom.:

AF XY:

0.000408

AC XY:

AN XY:

107934

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000230

Gnomad OTH exome

AF:

0.000196

GnomAD4 exome

AF:

0.000277

AC:

396

AN:

1430540

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

157

AN XY:

709208

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.000404

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000273

Gnomad4 OTH exome

AF:

0.000372

GnomAD4 genome

AF:

0.00293

AC:

446

AN:

152222

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.00318

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	MKS1: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 12, 2018	- -

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