17-5023901-C-G

Position:

• chr17-5023901-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006612.6(KIF1C):​c.3062C>G​(p.Pro1021Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF1C NM_006612.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2570681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.3062C>G	p.Pro1021Arg	missense_variant	23/23	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.3062C>G	p.Pro1021Arg	missense_variant	24/24		XP_005256481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.3062C>G	p.Pro1021Arg	missense_variant	23/23	1	NM_006612.6	ENSP00000320821.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399636 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 690110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	0.057
Eigen_PC	Benign	0.074
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.21
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.025	D
Polyphen		0.96	D
Vest4		0.26
MutPred		0.18		Gain of MoRF binding (P = 0.004);
MVP		0.72
MPC		1.0
ClinPred		0.63	D
GERP RS		4.8
Varity_R		0.054
gMVP		0.51

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: rs369620316; hg19: chr17-4927196;