chr17-58216279-CATTATAATACATCAAACTTTTGCTTCTGTAACTGTTTAATCAAATCAGTTCTACAGAACTGATGCTATCTGACATGTTTTCATAACCAACACTAAACTAATGAATGGCAGGGGAACCAAGAACATTAGAGCTAAAAGGAACCA-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP5_Moderate

The NM_017777.4(MKS1):​c.262-179_262-37del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 32)

Consequence

MKS1
NM_017777.4 intron

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.05

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • Meckel syndrome, type 1
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
  • Bardet-Biedl syndrome 13
    Inheritance: Unknown, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
  • Joubert syndrome 28
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • Bardet-Biedl syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Joubert syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Joubert syndrome with ocular defect
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Meckel syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP5
Variant 17-58216279-CATTATAATACATCAAACTTTTGCTTCTGTAACTGTTTAATCAAATCAGTTCTACAGAACTGATGCTATCTGACATGTTTTCATAACCAACACTAAACTAATGAATGGCAGGGGAACCAAGAACATTAGAGCTAAAAGGAACCA-C is Pathogenic according to our data. Variant chr17-58216279-CATTATAATACATCAAACTTTTGCTTCTGTAACTGTTTAATCAAATCAGTTCTACAGAACTGATGCTATCTGACATGTTTTCATAACCAACACTAAACTAATGAATGGCAGGGGAACCAAGAACATTAGAGCTAAAAGGAACCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 217674.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MKS1NM_017777.4 linkc.262-179_262-37del intron_variant Intron 3 of 17 ENST00000393119.7 NP_060247.2 Q9NXB0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MKS1ENST00000393119.7 linkc.262-179_262-37del intron_variant Intron 3 of 17 1 NM_017777.4 ENSP00000376827.2 Q9NXB0-1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Joubert syndrome Pathogenic:1
Feb 23, 2015
UW Hindbrain Malformation Research Program, University of Washington
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.0
BranchPoint Hunter
3.0
Mutation Taster
=9/91
disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1555600644; hg19: chr17-56293640; API