rs73345356

chr17-5022379-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006612.6(KIF1C):c.2298C>T(p.His766=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 1,581,366 control chromosomes in the GnomAD database, including 562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (286 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (276 hom.)
• Consequence: KIF1C NM_006612.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.196

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 17-5022379-C-T is Benign according to our data. Variant chr17-5022379-C-T is described in ClinVar as [Benign]. Clinvar id is 387794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.196 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1C	NM_006612.6	c.2298C>T	p.His766=	synonymous_variant	22/23	ENST00000320785.10
KIF1C	XM_005256424.3	c.2298C>T	p.His766=	synonymous_variant	23/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1C	ENST00000320785.10	c.2298C>T	p.His766=	synonymous_variant	22/23	1	NM_006612.6	P1

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5209 AN: 152256 Hom.: 285 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.0224

GnomAD3 exomes AF: 0.00920 AC: 1794 AN: 195036 Hom.: 88 AF XY: 0.00651 AC XY: 682 AN XY: 104694

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.00845

Gnomad ASJ exome AF: 0.000446

Gnomad EAS exome AF: 0.0000695

Gnomad SAS exome AF: 0.000266

Gnomad FIN exome AF: 0.0000552

Gnomad NFE exome AF: 0.00195

Gnomad OTH exome AF: 0.00662

GnomAD4 exome AF: 0.00504 AC: 7195 AN: 1428992 Hom.: 276 Cov.: 32 AF XY: 0.00453 AC XY: 3207 AN XY: 708168

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.00906

Gnomad4 ASJ exome AF: 0.000707

Gnomad4 EAS exome AF: 0.0000263

Gnomad4 SAS exome AF: 0.000386

Gnomad4 FIN exome AF: 0.000274

Gnomad4 NFE exome AF: 0.00202

Gnomad4 OTH exome AF: 0.00964

GnomAD4 genome AF: 0.0343 AC: 5219 AN: 152374 Hom.: 286 Cov.: 32 AF XY: 0.0324 AC XY: 2414 AN XY: 74510

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0151 Hom.: 47

Bravo AF: 0.0395

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 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	2.0
Dann	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs73345356; hg19: chr17-4925674;