rs145062338
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BS1BS2
The ENST00000455537.7(KIF5A):c.2412C>T(p.Asp804=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,614,000 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 3 hom. )
Consequence
KIF5A
ENST00000455537.7 synonymous
ENST00000455537.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.42
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 -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.17).
BP6
Variant 12-57578059-C-T is Benign according to our data. Variant chr12-57578059-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 240086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=3.42 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000452 (661/1461790) while in subpopulation MID AF= 0.00225 (13/5768). AF 95% confidence interval is 0.00133. There are 3 homozygotes in gnomad4_exome. There are 334 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 56 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIF5A | NM_004984.4 | c.2412C>T | p.Asp804= | synonymous_variant | 22/29 | ENST00000455537.7 | NP_004975.2 | |
KIF5A | NM_001354705.2 | c.2145C>T | p.Asp715= | synonymous_variant | 19/26 | NP_001341634.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF5A | ENST00000455537.7 | c.2412C>T | p.Asp804= | synonymous_variant | 22/29 | 1 | NM_004984.4 | ENSP00000408979 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000368 AC: 56AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000521 AC: 131AN: 251474Hom.: 1 AF XY: 0.000515 AC XY: 70AN XY: 135906
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GnomAD4 exome AF: 0.000452 AC: 661AN: 1461790Hom.: 3 Cov.: 31 AF XY: 0.000459 AC XY: 334AN XY: 727210
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GnomAD4 genome AF: 0.000368 AC: 56AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26AN XY: 74352
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | KIF5A: BP4, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 14, 2019 | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 09, 2017 | - - |
Hereditary spastic paraplegia 10 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 01, 2020 | - - |
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