rs201800868

chr17-5024111-G-Achr17-5024111-G-Cchr17-5024111-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_006612.6(KIF1C):c.3272G>A(p.Arg1091His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000832 in 1,610,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: KIF1C NM_006612.6 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 2.40

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.009293556).
• BP6: Variant 17-5024111-G-A is Benign according to our data. Variant chr17-5024111-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435640.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1C	NM_006612.6	c.3272G>A	p.Arg1091His	missense_variant	23/23	ENST00000320785.10
KIF1C	XM_005256424.3	c.3272G>A	p.Arg1091His	missense_variant	24/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1C	ENST00000320785.10	c.3272G>A	p.Arg1091His	missense_variant	23/23	1	NM_006612.6	P1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000290 AC: 70 AN: 241418 Hom.: 0 AF XY: 0.000312 AC XY: 41 AN XY: 131522

Gnomad AFR exome AF: 0.0000663

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00333

Gnomad SAS exome AF: 0.0000995

Gnomad FIN exome AF: 0.0000930

Gnomad NFE exome AF: 0.0000280

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000789 AC: 115 AN: 1458390 Hom.: 0 Cov.: 33 AF XY: 0.0000800 AC XY: 58 AN XY: 725430

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00157

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.0000664

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74428

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00233

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000813 Hom.: 1

Bravo AF: 0.000147

ExAC AF: 0.000215 AC: 26

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 12, 2016

- -

KIF1C-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 06, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Spastic ataxia 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.93	N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.19
Sift	Benign	0.061	T
Sift4G	Benign	0.36	T
Polyphen		0.93	P
Vest4		0.29
MVP		0.66
MPC		0.79
ClinPred		0.078	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.26

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: rs201800868; hg19: chr17-4927406;