17-5003999-A-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_006612.6(KIF1C):c.866A>C(p.Gln289Pro) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0014 in 1,613,864 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 4 hom. )
Consequence
KIF1C
NM_006612.6 missense, splice_region
NM_006612.6 missense, splice_region
Scores
3
9
7
Splicing: ADA: 0.8663
2
Clinical Significance
Conservation
PhyloP100: 4.03
Genes affected
KIF1C (HGNC:6317): (kinesin family member 1C) The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive. [provided by RefSeq, May 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.05489394).
BP6
?
Variant 17-5003999-A-C is Benign according to our data. Variant chr17-5003999-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 425119.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=1, Uncertain_significance=1}.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1C | NM_006612.6 | c.866A>C | p.Gln289Pro | missense_variant, splice_region_variant | 11/23 | ENST00000320785.10 | |
KIF1C | XM_005256424.3 | c.866A>C | p.Gln289Pro | missense_variant, splice_region_variant | 12/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1C | ENST00000320785.10 | c.866A>C | p.Gln289Pro | missense_variant, splice_region_variant | 11/23 | 1 | NM_006612.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00105 AC: 159AN: 152054Hom.: 1 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
159
AN:
152054
Hom.:
Cov.:
32
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: 0.00111 AC: 279AN: 251488Hom.: 2 AF XY: 0.00125 AC XY: 170AN XY: 135922
GnomAD3 exomes
AF:
AC:
279
AN:
251488
Hom.:
AF XY:
AC XY:
170
AN XY:
135922
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: 0.00144 AC: 2102AN: 1461692Hom.: 4 Cov.: 31 AF XY: 0.00146 AC XY: 1060AN XY: 727162
GnomAD4 exome
AF:
AC:
2102
AN:
1461692
Hom.:
Cov.:
31
AF XY:
AC XY:
1060
AN XY:
727162
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: 0.00104 AC: 159AN: 152172Hom.: 1 Cov.: 32 AF XY: 0.000874 AC XY: 65AN XY: 74392
GnomAD4 genome
?
AF:
AC:
159
AN:
152172
Hom.:
Cov.:
32
AF XY:
AC XY:
65
AN XY:
74392
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
4
ESP6500AA
AF:
AC:
3
ESP6500EA
AF:
AC:
19
ExAC
?
AF:
AC:
151
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 27, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | KIF1C: BS2 - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 12, 2016 | - - |
Spastic ataxia 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at