Variant 17-4999978-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006612.6(KIF1C):c.-28+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 469,290 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

KIF1C
NM_006612.6 splice_region, intron

Scores

Splicing: ADA: 0.0001321

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.709

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 17-4999978-G-A is Benign according to our data. Variant chr17-4999978-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 515316.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-4999978-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1C	NM_006612.6 linkuse as main transcript	c.-28+8G>A		splice_region_variant, intron_variant		ENST00000320785.10
KIF1C	XM_005256424.3 linkuse as main transcript	c.-28+8G>A		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1C	ENST00000320785.10 linkuse as main transcript	c.-28+8G>A		splice_region_variant, intron_variant		1	NM_006612.6	P1
KIF1C	ENST00000574165.1 linkuse as main transcript	c.-28+8G>A		splice_region_variant, intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000514

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000278

AC:

AN:

316922

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

AN XY:

166860

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000216

Gnomad4 NFE exome

AF:

0.000424

Gnomad4 OTH exome

AF:

0.000219

GnomAD4 genome

AF:

0.000256

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000514

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.000208

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 06, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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