rs192489748

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_006612.6(KIF1C):c.1165+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,614,186 control chromosomes in the GnomAD database, including 29 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 0.0043 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 27 hom. )

Consequence

KIF1C
NM_006612.6 splice_donor_region, intron

Scores

Splicing: ADA: 0.0001659

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 0.226

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 -9 ACMG points.

BP6

Variant 17-5005004-G-A is Benign according to our data. Variant chr17-5005004-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 445377.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=2, Uncertain_significance=2}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00432 (658/152350) while in subpopulation NFE AF= 0.00679 (462/68026). AF 95% confidence interval is 0.00628. There are 2 homozygotes in gnomad4. There are 318 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1C	NM_006612.6 linkuse as main transcript	c.1165+4G>A		splice_donor_region_variant, intron_variant		ENST00000320785.10
KIF1C	XM_005256424.3 linkuse as main transcript	c.1165+4G>A		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1C	ENST00000320785.10 linkuse as main transcript	c.1165+4G>A		splice_donor_region_variant, intron_variant		1	NM_006612.6	P1

Frequencies

GnomAD3 genomes

AF:

0.00433

AC:

659

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00743

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00681

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00467

AC:

1172

AN:

251166

Hom.:

AF XY:

0.00470

AC XY:

638

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00904

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00758

Gnomad NFE exome

AF:

0.00711

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00556

AC:

8134

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00547

AC XY:

3976

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00972

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00822

Gnomad4 NFE exome

AF:

0.00629

Gnomad4 OTH exome

AF:

0.00505

GnomAD4 genome

AF:

0.00432

AC:

658

AN:

152350

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00743

Gnomad4 NFE

AF:

0.00679

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00597

Hom.:

Bravo

AF:

0.00357

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00664

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	KIF1C: BS2 -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 05, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 31, 2020	- -

Hereditary spastic paraplegia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Sep 04, 2020

- -

Spastic ataxia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

Cadd

Benign

Dann

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.30

Position offset: 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