chr2-240788103-G-A
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5
The NM_001244008.2(KIF1A):c.311C>T(p.Ser104Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
KIF1A
NM_001244008.2 missense
NM_001244008.2 missense
Scores
11
2
1
Clinical Significance
Conservation
PhyloP100: 6.54
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 Pathogenic. Variant got 10 ACMG points.
PM1
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_001244008.2
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, KIF1A
PP3
MetaRNN computational evidence supports a deleterious effect, 0.978
PP5
Variant 2-240788103-G-A is Pathogenic according to our data. Variant chr2-240788103-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435632.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.311C>T | p.Ser104Phe | missense_variant | 4/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.311C>T | p.Ser104Phe | missense_variant | 4/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 37
GnomAD4 exome
Cov.:
37
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 30 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Paris Brain Institute, Inserm - ICM | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 29, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;.;.;.;.;D;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;.;.;.;.;.;H;.;.;.;H;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Polyphen
D;.;.;.;.;.;.;D;.;.;.;D;.
Vest4
0.96, 0.97
MutPred
Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);Loss of disorder (P = 0.0038);
MVP
0.97
MPC
2.5
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