rs886038761
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_ModerateBP6_Very_Strong
The NM_198525.3(KIF7):c.3589C>T(p.Leu1197=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000434 in 1,613,488 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
KIF7
NM_198525.3 synonymous
NM_198525.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.64
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]
TICRR (HGNC:28704): (TOPBP1 interacting checkpoint and replication regulator) Enables chromatin binding activity. Involved in regulation of DNA-dependent DNA replication initiation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 15-89629051-G-A is Benign according to our data. Variant chr15-89629051-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF7 | NM_198525.3 | c.3589C>T | p.Leu1197= | synonymous_variant | 18/19 | ENST00000394412.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF7 | ENST00000394412.8 | c.3589C>T | p.Leu1197= | synonymous_variant | 18/19 | 5 | NM_198525.3 | P2 | |
TICRR | ENST00000561095.1 | c.*97-379G>A | intron_variant, NMD_transcript_variant | 1 | |||||
KIF7 | ENST00000696512.1 | c.3712C>T | p.Leu1238= | synonymous_variant | 18/19 | A2 | |||
KIF7 | ENST00000677187.1 | n.1263C>T | non_coding_transcript_exon_variant | 6/7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151508Hom.: 0 Cov.: 27
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461864Hom.: 0 Cov.: 36 AF XY: 0.00000550 AC XY: 4AN XY: 727236
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151624Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 74068
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Acrocallosal syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 02, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at