chr12-57550276-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM1PP2BP4BS2
The NM_004984.4(KIF5A):c.5C>T(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,613,984 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2K) has been classified as Uncertain significance.
Frequency
Consequence
NM_004984.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF5A | NM_004984.4 | c.5C>T | p.Ala2Val | missense_variant | 1/29 | ENST00000455537.7 | |
KIF5A | NM_001354705.2 | c.5C>T | p.Ala2Val | missense_variant | 1/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF5A | ENST00000455537.7 | c.5C>T | p.Ala2Val | missense_variant | 1/29 | 1 | NM_004984.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251214Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135832
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461776Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727180
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2 of the KIF5A protein (p.Ala2Val). This variant is present in population databases (rs780433858, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KIF5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1521590). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KIF5A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.5C>T (p.A2V) alteration is located in exon 1 (coding exon 1) of the KIF5A gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | KIF5A: PP2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at