2-240719128-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001244008.2(KIF1A):c.5092G>A(p.Val1698Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,612,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
KIF1A
NM_001244008.2 missense
NM_001244008.2 missense
Scores
3
5
6
Clinical Significance
Conservation
PhyloP100: 4.68
Genes affected
KIF1A (HGNC:888): (kinesin family member 1A) The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP2
Missense variant where missense usually causes diseases, KIF1A
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.5092G>A | p.Val1698Met | missense_variant | 47/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.5092G>A | p.Val1698Met | missense_variant | 47/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152184Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
8
AN:
152184
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 248216Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134856
GnomAD3 exomes
AF:
AC:
6
AN:
248216
Hom.:
AF XY:
AC XY:
4
AN XY:
134856
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1460252Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 726400
GnomAD4 exome
AF:
AC:
44
AN:
1460252
Hom.:
Cov.:
31
AF XY:
AC XY:
24
AN XY:
726400
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74342
GnomAD4 genome
AF:
AC:
8
AN:
152184
Hom.:
Cov.:
33
AF XY:
AC XY:
7
AN XY:
74342
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
3
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 07, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 03, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21376300, 21820098, 26125038) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 20, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2021 | The c.4789G>A (p.V1597M) alteration is located in exon 45 (coding exon 44) of the KIF1A gene. This alteration results from a G to A substitution at nucleotide position 4789, causing the valine (V) at amino acid position 1597 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;.;.;.;.;D;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.;.;.;M;.;.;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Polyphen
D;.;.;.;.;.;.;D;.;.;.;.;.;.
Vest4
0.83
MutPred
Gain of MoRF binding (P = 0.0783);.;.;.;.;.;.;Gain of MoRF binding (P = 0.0783);.;.;.;.;.;.;
MVP
0.41
MPC
1.3
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at