rs35919356

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006612.6(KIF1C):c.1293G>A(p.Thr431Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,606,784 control chromosomes in the GnomAD database, including 451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 27 hom., cov: 31)

Exomes 𝑓: 0.021 ( 424 hom. )

Consequence

KIF1C
NM_006612.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.647

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-5007042-G-A is Benign according to our data. Variant chr17-5007042-G-A is described in ClinVar as [Benign]. Clinvar id is 380883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.647 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0147 (2245/152216) while in subpopulation NFE AF= 0.0231 (1571/68020). AF 95% confidence interval is 0.0221. There are 27 homozygotes in gnomad4. There are 1055 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6 link	c.1293G>A	p.Thr431Thr	synonymous_variant	Exon 14 of 23	ENST00000320785.10	NP_006603.2	O43896
KIF1C	XM_005256424.3 link	c.1293G>A	p.Thr431Thr	synonymous_variant	Exon 15 of 24		XP_005256481.1	O43896

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10 link	c.1293G>A	p.Thr431Thr	synonymous_variant	Exon 14 of 23	1	NM_006612.6	ENSP00000320821.5		O43896

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2244

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0231

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0173

AC:

4137

AN:

239110

Hom.:

AF XY:

0.0178

AC XY:

2303

AN XY:

129728

show subpopulations

Gnomad AFR exome

AF:

0.00352

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.00652

Gnomad EAS exome

AF:

0.0000572

Gnomad SAS exome

AF:

0.0153

Gnomad FIN exome

AF:

0.0193

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0215

AC:

31273

AN:

1454568

Hom.:

424

Cov.:

AF XY:

0.0213

AC XY:

15406

AN XY:

723796

show subpopulations

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.00665

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0143

Gnomad4 FIN exome

AF:

0.0210

Gnomad4 NFE exome

AF:

0.0244

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0147

AC:

2245

AN:

152216

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1055

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00371

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0129

Gnomad4 FIN

AF:

0.0174

Gnomad4 NFE

AF:

0.0231

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0180

Hom.:

Bravo

AF:

0.0136

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.0214

EpiControl

AF:

0.0198

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 30, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Spastic ataxia 2

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia

Benign:1

Nov 11, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

DANN

Benign

0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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