rs79290524

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1

The NM_006612.6(KIF1C):ā€‹c.1136C>Gā€‹(p.Ala379Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000499 in 1,614,240 control chromosomes in the GnomAD database, including 1 homozygotes. 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: š‘“ 0.00032 ( 0 hom., cov: 32)
Exomes š‘“: 0.00052 ( 1 hom. )

Consequence

KIF1C
NM_006612.6 missense

Scores

1
5
13

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 4.95
Variant links:
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 17-5004971-C-G is Benign according to our data. Variant chr17-5004971-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 468849.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000322 (49/152362) while in subpopulation NFE AF= 0.000603 (41/68032). AF 95% confidence interval is 0.000457. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF1CNM_006612.6 linkc.1136C>G p.Ala379Gly missense_variant Exon 13 of 23 ENST00000320785.10 NP_006603.2 O43896
KIF1CXM_005256424.3 linkc.1136C>G p.Ala379Gly missense_variant Exon 14 of 24 XP_005256481.1 O43896

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF1CENST00000320785.10 linkc.1136C>G p.Ala379Gly missense_variant Exon 13 of 23 1 NM_006612.6 ENSP00000320821.5 O43896

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000723
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000603
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000422
AC:
106
AN:
251392
Hom.:
1
AF XY:
0.000456
AC XY:
62
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000721
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000518
AC:
757
AN:
1461878
Hom.:
1
Cov.:
32
AF XY:
0.000534
AC XY:
388
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000278
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000621
Gnomad4 OTH exome
AF:
0.000464
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152362
Hom.:
0
Cov.:
32
AF XY:
0.000336
AC XY:
25
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000603
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000626
Hom.:
1
Bravo
AF:
0.000306
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000544
AC:
66
EpiCase
AF:
0.000436
EpiControl
AF:
0.000356

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenNov 01, 2019- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2022KIF1C: PP3 -
Spastic ataxia 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 13, 2025- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
33
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.47
T
Eigen
Benign
-0.072
Eigen_PC
Benign
0.061
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.096
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.79
N
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.2
D
REVEL
Benign
0.18
Sift
Benign
0.16
T
Sift4G
Benign
0.19
T
Polyphen
0.58
P
Vest4
0.38
MVP
0.65
MPC
0.40
ClinPred
0.032
T
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.12
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.92
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.92
Position offset: -1
DS_DL_spliceai
0.23
Position offset: 29

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs79290524; hg19: chr17-4908266; API