rs754172009
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BP6
The NM_001244008.2(KIF1A):c.4229G>T(p.Gly1410Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,608,186 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
KIF1A
NM_001244008.2 missense
NM_001244008.2 missense
Scores
11
3
Clinical Significance
Conservation
PhyloP100: 7.61
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, KIF1A
BP4
?
Computational evidence support a benign effect (MetaRNN=0.38941562).
BP6
?
Variant 2-240725298-C-A is Benign according to our data. Variant chr2-240725298-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 580895.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.4229G>T | p.Gly1410Val | missense_variant | 40/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.4229G>T | p.Gly1410Val | missense_variant | 40/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000376 AC: 9AN: 239638Hom.: 0 AF XY: 0.0000460 AC XY: 6AN XY: 130570
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GnomAD4 exome AF: 0.0000213 AC: 31AN: 1456062Hom.: 0 Cov.: 31 AF XY: 0.0000276 AC XY: 20AN XY: 723824
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74302
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 05, 2021 | The p.G1410V variant (also known as c.4229G>T), located in coding exon 39 of the KIF1A gene, results from a G to T substitution at nucleotide position 4229. The glycine at codon 1410 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, 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 | Oct 03, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.;.;.;D;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.;.;.;.;.;M;.;.;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
D;.;.;.;.;.;.;D;.;.;.;.;.;D
Vest4
0.71
MutPred
Gain of helix (P = 0.0128);.;.;.;.;.;.;Gain of helix (P = 0.0128);.;.;.;.;.;.;
MVP
0.60
MPC
0.89
ClinPred
T
GERP RS
Varity_R
gMVP
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