rs79290524

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS1

The NM_006612.6(KIF1C):c.1136C>G(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: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 1 hom. )

Consequence

KIF1C
NM_006612.6 missense

Scores

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]

KIF1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6 link	c.1136C>G	p.Ala379Gly	missense_variant	Exon 13 of 23	ENST00000320785.10	NP_006603.2	O43896
KIF1C	XM_005256424.3 link	c.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
KIF1C	ENST00000320785.10 link	c.1136C>G	p.Ala379Gly	missense_variant	Exon 13 of 23	1	NM_006612.6	ENSP00000320821.5		O43896

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152244

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000422

AC:

106

AN:

251392

AF XY:

0.000456

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 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.:

Cov.:

AF XY:

0.000534

AC XY:

388

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.000112

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.000278

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.0000749

AC:

AN:

53410

Gnomad4 NFE exome

AF:

0.000621

AC:

691

AN:

1112006

Gnomad4 Remaining exome

AF:

0.000464

AC:

AN:

60396

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

110

<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:

0.000322

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0000721

AC:

0.0000721362

AN:

0.0000721362

Gnomad4 AMR

AF:

0.000196

AC:

0.000195976

AN:

0.000195976

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000414

AC:

0.000414422

AN:

0.000414422

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000603

AC:

0.000602658

AN:

0.000602658

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.000626

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000544

AC:

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

Nov 01, 2019

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIF1C: PP3 -

Spastic ataxia 2

Benign:1

Jan 13, 2025

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

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.072

Eigen_PC

Benign

0.061

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.027

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.79

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.18

Sift

Benign

0.16

Sift4G

Benign

0.19

Polyphen

0.58

Vest4

0.38

MVP

0.65

MPC

0.40

ClinPred

0.032

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.12

gMVP

0.48

Mutation Taster

=92/8

polymorphism

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.

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