chr17-5023565-C-A

Position:

• chr17-5023565-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006612.6(KIF1C):​c.2726C>A​(p.Pro909Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,613,566 control chromosomes in the GnomAD database, including 402 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (223 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (179 hom.)
• Consequence: KIF1C NM_006612.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.10

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 (MetaRNN=0.002075553).
• BP6: Variant 17-5023565-C-A is Benign according to our data. Variant chr17-5023565-C-A is described in ClinVar as [Benign]. Clinvar id is 383663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.2726C>A	p.Pro909Gln	missense_variant	23/23	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.2726C>A	p.Pro909Gln	missense_variant	24/24		XP_005256481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.2726C>A	p.Pro909Gln	missense_variant	23/23	1	NM_006612.6	ENSP00000320821	P1

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4488 AN: 152060 Hom.: 223 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0191

GnomAD3 exomes AF: 0.00819 AC: 2028 AN: 247538 Hom.: 113 AF XY: 0.00614 AC XY: 826 AN XY: 134454

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00705

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000154

Gnomad OTH exome AF: 0.00345

GnomAD4 exome AF: 0.00288 AC: 4214 AN: 1461388 Hom.: 179 Cov.: 31 AF XY: 0.00245 AC XY: 1779 AN XY: 727010

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00718

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000935

Gnomad4 OTH exome AF: 0.00624

GnomAD4 genome AF: 0.0295 AC: 4491 AN: 152178 Hom.: 223 Cov.: 32 AF XY: 0.0284 AC XY: 2115 AN XY: 74390

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.00968

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0138 Hom.: 29

Bravo AF: 0.0331

ESP6500AA AF: 0.0992 AC: 437

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0101 AC: 1226

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Hereditary spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.13
Sift	Benign	0.030	D
Sift4G	Uncertain	0.017	D
Polyphen		0.61	P
Vest4		0.087
MPC		0.34
ClinPred		0.011	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.25

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: rs78970955; hg19: chr17-4926860;