rs114935927

chr17-5006907-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006612.6(KIF1C):c.1166-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,611,400 control chromosomes in the GnomAD database, including 48 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (25 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (23 hom.)
• Consequence: KIF1C NM_006612.6 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002593
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.176

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-5006907-C-T is Benign according to our data. Variant chr17-5006907-C-T is described in ClinVar as [Benign]. Clinvar id is 468850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-5006907-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00965 (1469/152258) while in subpopulation AFR AF= 0.0334 (1389/41538). AF 95% confidence interval is 0.032. There are 25 homozygotes in gnomad4. There are 668 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1C	NM_006612.6	c.1166-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000320785.10
KIF1C	XM_005256424.3	c.1166-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1C	ENST00000320785.10	c.1166-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006612.6	P1

Frequencies

GnomAD3 genomes AF: 0.00966 AC: 1469 AN: 152140 Hom.: 25 Cov.: 31

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00259 AC: 643 AN: 248038 Hom.: 13 AF XY: 0.00192 AC XY: 258 AN XY: 134318

Gnomad AFR exome AF: 0.0336

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.000401

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000991

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00106 AC: 1540 AN: 1459142 Hom.: 23 Cov.: 31 AF XY: 0.000931 AC XY: 676 AN XY: 726014

Gnomad4 AFR exome AF: 0.0352

Gnomad4 AMR exome AF: 0.00198

Gnomad4 ASJ exome AF: 0.000652

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000855

Gnomad4 OTH exome AF: 0.00249

GnomAD4 genome AF: 0.00965 AC: 1469 AN: 152258 Hom.: 25 Cov.: 31 AF XY: 0.00897 AC XY: 668 AN XY: 74452

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00331 Hom.: 0

Bravo AF: 0.0116

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000475

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 23, 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. -

Spastic ataxia 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Hereditary spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jun 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.58
Dann	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs114935927; hg19: chr17-4910202;