rs146628704

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_006612.6(KIF1C):c.2591G>A(p.Arg864His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000997 in 1,574,914 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 Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

KIF1C
NM_006612.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 0.883

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: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16502282).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000131 (20/152250) while in subpopulation NFE AF = 0.000191 (13/68034). AF 95% confidence interval is 0.000112. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006612.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	NM_006612.6	MANE Select	c.2591G>A	p.Arg864His	missense	Exon 22 of 23	NP_006603.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.2591G>A	p.Arg864His	missense	Exon 22 of 23	ENSP00000320821.5	O43896
KIF1C	ENST00000948910.1		c.2621G>A	p.Arg874His	missense	Exon 22 of 23	ENSP00000618969.1
KIF1C	ENST00000948913.1		c.2621G>A	p.Arg874His	missense	Exon 21 of 22	ENSP00000618972.1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000105

AC:

AN:

209524

AF XY:

0.000115

show subpopulations

Gnomad AFR exome

AF:

0.0000671

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000143

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000963

AC:

137

AN:

1422664

Hom.:

Cov.:

AF XY:

0.0000938

AC XY:

AN XY:

703598

show subpopulations

African (AFR)

AF:

0.0000919

AC:

AN:

32640

American (AMR)

AF:

0.0000739

AC:

AN:

40620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23544

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39246

South Asian (SAS)

AF:

0.000100

AC:

AN:

79684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49870

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.000107

AC:

117

AN:

1092724

Other (OTH)

AF:

0.0000851

AC:

AN:

58732

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

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:

0.000131

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41472

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.0000529

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000231

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia (1)

not provided (1)

not specified (1)

Spastic ataxia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

0.15

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.048

MetaRNN

Benign

0.17

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.6

PhyloP100

0.88

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.3

REVEL

Benign

0.23

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.44

MVP

0.75

MPC

1.1

ClinPred

0.13

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.11

gMVP

0.40

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over