chr17-5003999-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

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

Scores

Splicing: ADA: 0.8663

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 4.03

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]

KIF1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 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: {Uncertain_significance=1, Likely_benign=2, Benign=1}.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00104 (159/152172) while in subpopulation NFE AF = 0.00199 (135/68000). AF 95% confidence interval is 0.00171. There are 1 homozygotes in GnomAd4. There are 65 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6 link	c.866A>C	p.Gln289Pro	missense_variant, splice_region_variant	Exon 11 of 23	ENST00000320785.10	NP_006603.2	O43896
KIF1C	XM_005256424.3 link	c.866A>C	p.Gln289Pro	missense_variant, splice_region_variant	Exon 12 of 24		XP_005256481.1	O43896

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10 link	c.866A>C	p.Gln289Pro	missense_variant, splice_region_variant	Exon 11 of 23	1	NM_006612.6	ENSP00000320821.5		O43896

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

159

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00111

AC:

279

AN:

251488

AF XY:

0.00125

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000970

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00144

AC:

2102

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1060

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

AC:

AN:

33472

Gnomad4 AMR exome

AF:

0.000335

AC:

AN:

44718

Gnomad4 ASJ exome

AF:

0.000421

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.000765

AC:

AN:

86256

Gnomad4 FIN exome

AF:

0.000618

AC:

AN:

53416

Gnomad4 NFE exome

AF:

0.00169

AC:

1879

AN:

1111840

Gnomad4 Remaining exome

AF:

0.00121

AC:

AN:

60386

Heterozygous variant carriers

102

204

307

409

511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00104

AC:

159

AN:

152172

Hom.:

Cov.:

AF XY:

0.000874

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000145

AC:

0.000144606

AN:

0.000144606

Gnomad4 AMR

AF:

0.000523

AC:

0.000523286

AN:

0.000523286

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000415

AC:

0.00041511

AN:

0.00041511

Gnomad4 FIN

AF:

0.000566

AC:

0.000565824

AN:

0.000565824

Gnomad4 NFE

AF:

0.00199

AC:

0.00198529

AN:

0.00198529

Gnomad4 OTH

AF:

0.000947

AC:

0.00094697

AN:

0.00094697

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.000994

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00124

AC:

151

EpiCase

AF:

0.00229

EpiControl

AF:

0.00184

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

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIF1C: BS2 -

Jul 27, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia

Uncertain:1

Dec 12, 2016

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spastic ataxia 2

Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.055

MetaSVM

Uncertain

0.59

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.0

REVEL

Pathogenic

0.74

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.027

Polyphen

0.97

Vest4

0.31

MVP

0.91

MPC

1.0

ClinPred

0.068

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.65

Mutation Taster

=34/66

disease causing

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.87

dbscSNV1_RF

Benign

0.63

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over