rs797044466
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_198525.3(KIF7):c.811del(p.Glu271ArgfsTer51) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,547,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
KIF7
NM_198525.3 frameshift
NM_198525.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.62
Genes affected
KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-89649085-TC-T is Pathogenic according to our data. Variant chr15-89649085-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 30901.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF7 | NM_198525.3 | c.811del | p.Glu271ArgfsTer51 | frameshift_variant | 4/19 | ENST00000394412.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF7 | ENST00000394412.8 | c.811del | p.Glu271ArgfsTer51 | frameshift_variant | 4/19 | 5 | NM_198525.3 | P2 | |
KIF7 | ENST00000445906.1 | c.*470del | 3_prime_UTR_variant, NMD_transcript_variant | 4/5 | 1 | ||||
KIF7 | ENST00000696512.1 | c.934del | p.Glu312ArgfsTer51 | frameshift_variant | 4/19 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151904Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000215 AC: 3AN: 1395878Hom.: 0 Cov.: 34 AF XY: 0.00000290 AC XY: 2AN XY: 688640
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151904Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74162
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Joubert syndrome 12/15, digenic Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 15, 2012 | - - |
Joubert syndrome 12 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 15, 2012 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at