rs57144955

chr17-5014827-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006612.6(KIF1C):c.1656A>G(p.Pro552=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 1,591,798 control chromosomes in the GnomAD database, including 593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (303 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (290 hom.)
• Consequence: KIF1C NM_006612.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.81

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=-0.87).
• BP6: Variant 17-5014827-A-G is Benign according to our data. Variant chr17-5014827-A-G is described in ClinVar as [Benign]. Clinvar id is 387793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1C	NM_006612.6	c.1656A>G	p.Pro552=	synonymous_variant	18/23	ENST00000320785.10
KIF1C	XM_005256424.3	c.1656A>G	p.Pro552=	synonymous_variant	19/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1C	ENST00000320785.10	c.1656A>G	p.Pro552=	synonymous_variant	18/23	1	NM_006612.6	P1
KIF1C	ENST00000573815.1	n.198A>G		non_coding_transcript_exon_variant	2/6	5

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5300 AN: 152156 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.00875 AC: 1859 AN: 212502 Hom.: 93 AF XY: 0.00606 AC XY: 685 AN XY: 113114

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.00818

Gnomad ASJ exome AF: 0.000436

Gnomad EAS exome AF: 0.0000615

Gnomad SAS exome AF: 0.000233

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000454

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00373 AC: 5376 AN: 1439524 Hom.: 290 Cov.: 30 AF XY: 0.00325 AC XY: 2318 AN XY: 713444

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.00881

Gnomad4 ASJ exome AF: 0.000705

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000365

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000254

Gnomad4 OTH exome AF: 0.00878

GnomAD4 genome AF: 0.0349 AC: 5309 AN: 152274 Hom.: 303 Cov.: 32 AF XY: 0.0328 AC XY: 2442 AN XY: 74460

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0156 Hom.: 53

Bravo AF: 0.0402

Asia WGS AF: 0.00693 AC: 26 AN: 3478

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

Aug 16, 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 31, 2024

- -

Hereditary spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.4
Dann	Benign	0.65

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: rs57144955; hg19: chr17-4918122;