rs35919356

chr17-5007042-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006612.6(KIF1C):c.1293G>A(p.Thr431=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.647

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 -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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1C	NM_006612.6	c.1293G>A	p.Thr431=	synonymous_variant	14/23	ENST00000320785.10
KIF1C	XM_005256424.3	c.1293G>A	p.Thr431=	synonymous_variant	15/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1C	ENST00000320785.10	c.1293G>A	p.Thr431=	synonymous_variant	14/23	1	NM_006612.6	P1

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2244 AN: 152098 Hom.: 27 Cov.: 31

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.: 64 AF XY: 0.0178 AC XY: 2303 AN XY: 129728

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.: 32 AF XY: 0.0213 AC XY: 15406 AN XY: 723796

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.: 27 Cov.: 31 AF XY: 0.0142 AC XY: 1055 AN XY: 74414

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.: 18

Bravo AF: 0.0136

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.0214

EpiControl AF: 0.0198

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

Jun 30, 2016

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 29, 2024

- -

Hereditary spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Nov 11, 2021

- -

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

Other links and lift over

dbSNP: rs35919356; hg19: chr17-4910337;