rs747424547

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS1

The NM_006612.6(KIF1C):c.14C>T(p.Ser5Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000572 in 1,573,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S5S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

KIF1C
NM_006612.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.70

Publications

0 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 Gene-Disease associations (from GenCC):

spastic ataxia 2
Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

KIF1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.782

BP6

Variant 17-5000260-C-T is Benign according to our data. Variant chr17-5000260-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 565364.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000394 (6/152160) while in subpopulation SAS AF = 0.000414 (2/4832). AF 95% confidence interval is 0.0000729. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6 link	c.14C>T	p.Ser5Leu	missense_variant	Exon 3 of 23	ENST00000320785.10	NP_006603.2	O43896
KIF1C	XM_005256424.3 link	c.14C>T	p.Ser5Leu	missense_variant	Exon 4 of 24		XP_005256481.1	O43896

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10 link	c.14C>T	p.Ser5Leu	missense_variant	Exon 3 of 23	1	NM_006612.6	ENSP00000320821.5		O43896
KIF1C	ENST00000574165.1 link	c.14C>T	p.Ser5Leu	missense_variant	Exon 4 of 7	5		ENSP00000458697.1		I3L1B1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000953

AC:

AN:

188804

AF XY:

0.000109

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000362

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.0000732

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000369

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000591

AC:

AN:

1421606

Hom.:

Cov.:

AF XY:

0.0000597

AC XY:

AN XY:

703734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32250

American (AMR)

AF:

0.0000260

AC:

AN:

38498

Ashkenazi Jewish (ASJ)

AF:

0.000983

AC:

AN:

25424

East Asian (EAS)

AF:

0.0000812

AC:

AN:

36968

South Asian (SAS)

AF:

0.000148

AC:

AN:

80888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5486

European-Non Finnish (NFE)

AF:

0.0000339

AC:

AN:

1092772

Other (OTH)

AF:

0.000102

AC:

AN:

58894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.0000394

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000103

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000670

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spastic ataxia 2

Benign:1

Aug 10, 2022

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

Pathogenic

0.64

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.72

D;.

Eigen

Pathogenic

0.80

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Pathogenic

0.45

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Pathogenic

0.98

MutationAssessor

Uncertain

2.8

M;.

PhyloP100

7.7

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.7

D;.

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;.

Vest4

0.83

MutPred

0.42

Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);

MVP

0.96

MPC

0.99

ClinPred

0.81

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.74

gMVP

0.76

Mutation Taster

=49/51

disease causing

(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