NM_006612.6:c.3272G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_006612.6(KIF1C):c.3272G>A(p.Arg1091His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000832 in 1,610,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

KIF1C
NM_006612.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.40

Publications

2 publications found

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:

KIF1C-AS1 (HGNC:40324): (KIF1C antisense RNA 1)

KIF1C-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009293556).

BP6

Variant 17-5024111-G-A is Benign according to our data. Variant chr17-5024111-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 435640.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000125 (19/152216) while in subpopulation EAS AF = 0.00233 (12/5160). AF 95% confidence interval is 0.00134. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6 link	c.3272G>A	p.Arg1091His	missense_variant	Exon 23 of 23	ENST00000320785.10	NP_006603.2	O43896
KIF1C	XM_005256424.3 link	c.3272G>A	p.Arg1091His	missense_variant	Exon 24 of 24		XP_005256481.1	O43896

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10 link	c.3272G>A	p.Arg1091His	missense_variant	Exon 23 of 23	1	NM_006612.6	ENSP00000320821.5		O43896
KIF1C-AS1	ENST00000438266.2 link	n.172-3156C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000290

AC:

AN:

241418

AF XY:

0.000312

show subpopulations

Gnomad AFR exome

AF:

0.0000663

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.0000930

Gnomad NFE exome

AF:

0.0000280

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000789

AC:

115

AN:

1458390

Hom.:

Cov.:

AF XY:

0.0000800

AC XY:

AN XY:

725430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33350

American (AMR)

AF:

0.0000226

AC:

AN:

44316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25942

East Asian (EAS)

AF:

0.00157

AC:

AN:

39480

South Asian (SAS)

AF:

0.0000698

AC:

AN:

85934

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52920

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1110468

Other (OTH)

AF:

0.0000664

AC:

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000125

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41528

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00233

AC:

AN:

5160

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000431

Hom.:

Bravo

AF:

0.000147

ExAC

AF:

0.000215

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 12, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

KIF1C-related disorder

Benign:1

Aug 06, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Spastic ataxia 2

Benign:1

Oct 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.0093

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

PhyloP100

2.4

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.89

REVEL

Benign

0.19

Sift

Benign

0.061

Sift4G

Benign

0.36

Polyphen

0.93

Vest4

0.29

MVP

0.66

MPC

0.79

ClinPred

0.078

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.26

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over