rs181688415
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004984.4(KIF5A):c.820-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,140 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0073 ( 7 hom., cov: 32)
Exomes 𝑓: 0.012 ( 126 hom. )
Consequence
KIF5A
NM_004984.4 intron
NM_004984.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0940
Genes affected
KIF5A (HGNC:6323): (kinesin family member 5A) This gene encodes a member of the kinesin family of proteins. Members of this family are part of a multisubunit complex that functions as a microtubule motor in intracellular organelle transport. Mutations in this gene cause autosomal dominant spastic paraplegia 10. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 12-57569237-G-T is Benign according to our data. Variant chr12-57569237-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 382750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57569237-G-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00732 (1111/151796) while in subpopulation NFE AF= 0.0126 (854/67962). AF 95% confidence interval is 0.0119. There are 7 homozygotes in gnomad4. There are 526 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1111 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF5A | NM_004984.4 | c.820-19G>T | intron_variant | ENST00000455537.7 | |||
KIF5A | NM_001354705.2 | c.553-19G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF5A | ENST00000455537.7 | c.820-19G>T | intron_variant | 1 | NM_004984.4 | P1 | |||
KIF5A | ENST00000286452.5 | c.553-19G>T | intron_variant | 2 | |||||
KIF5A | ENST00000674619.1 | c.820-19G>T | intron_variant | ||||||
KIF5A | ENST00000676457.1 | c.715-19G>T | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00732 AC: 1111AN: 151678Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.00789 AC: 1982AN: 251304Hom.: 16 AF XY: 0.00844 AC XY: 1146AN XY: 135838
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GnomAD4 exome AF: 0.0115 AC: 16876AN: 1461344Hom.: 126 Cov.: 32 AF XY: 0.0116 AC XY: 8416AN XY: 727030
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GnomAD4 genome ? AF: 0.00732 AC: 1111AN: 151796Hom.: 7 Cov.: 32 AF XY: 0.00709 AC XY: 526AN XY: 74144
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 18, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 02, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 30, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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