rs387907044
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_198525.3(KIF7):c.460C>T(p.Arg154Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000357 in 1,399,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Consequence
KIF7
NM_198525.3 stop_gained
NM_198525.3 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 5.01
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 15-89649810-G-A is Pathogenic according to our data. Variant chr15-89649810-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 30896.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.460C>T | p.Arg154Ter | stop_gained | 3/19 | ENST00000394412.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF7 | ENST00000394412.8 | c.460C>T | p.Arg154Ter | stop_gained | 3/19 | 5 | NM_198525.3 | P2 | |
KIF7 | ENST00000445906.1 | c.*119C>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/5 | 1 | ||||
KIF7 | ENST00000696512.1 | c.583C>T | p.Arg195Ter | stop_gained | 3/19 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000637 AC: 1AN: 156908Hom.: 0 AF XY: 0.0000120 AC XY: 1AN XY: 83102
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GnomAD4 exome AF: 0.00000357 AC: 5AN: 1399446Hom.: 0 Cov.: 31 AF XY: 0.00000435 AC XY: 3AN XY: 690238
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GnomAD4 genome ? Cov.: 33
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Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Acrocallosal syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2011 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at