rs975756878
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_198525.3(KIF7):c.1164C>T(p.Gly388Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000906 in 1,214,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000056 ( 0 hom. )
Consequence
KIF7
NM_198525.3 synonymous
NM_198525.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.271
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 15-89648534-G-A is Benign according to our data. Variant chr15-89648534-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 582482.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=0.271 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIF7 | NM_198525.3 | c.1164C>T | p.Gly388Gly | synonymous_variant | 5/19 | ENST00000394412.8 | NP_940927.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF7 | ENST00000394412.8 | c.1164C>T | p.Gly388Gly | synonymous_variant | 5/19 | 5 | NM_198525.3 | ENSP00000377934.3 | ||
KIF7 | ENST00000445906.1 | n.*823C>T | non_coding_transcript_exon_variant | 5/5 | 1 | ENSP00000395906.1 | ||||
KIF7 | ENST00000445906.1 | n.*823C>T | 3_prime_UTR_variant | 5/5 | 1 | ENSP00000395906.1 | ||||
KIF7 | ENST00000696512.1 | c.1287C>T | p.Gly429Gly | synonymous_variant | 5/19 | ENSP00000512678.1 |
Frequencies
GnomAD3 genomes AF: 0.0000339 AC: 5AN: 147398Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000776 AC: 1AN: 12894Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 8146
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GnomAD4 exome AF: 0.00000562 AC: 6AN: 1066864Hom.: 0 Cov.: 27 AF XY: 0.00000389 AC XY: 2AN XY: 514772
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GnomAD4 genome AF: 0.0000339 AC: 5AN: 147398Hom.: 0 Cov.: 32 AF XY: 0.0000418 AC XY: 3AN XY: 71748
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 03, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 12, 2019 | - - |
KIF7-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 05, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Acrocallosal syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 04, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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