rs3217067

chr17-58212356-TGCA-Tchr17-58212356-TGCA-TGCAGCA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_017777.4(MKS1):c.915+19_915+21del 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.61

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]

ACMG classification

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	UniProt
MKS1	NM_017777.4	c.915+19_915+21del		intron_variant		ENST00000393119.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKS1	ENST00000393119.7	c.915+19_915+21del		intron_variant		1	NM_017777.4	P1

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12704 AN: 152152 Hom.: 577 Cov.: 31

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

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

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.: 31 AF XY: 0.0850 AC XY: 6332 AN XY: 74452

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

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

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3217067; hg19: chr17-56289717;