17-5022672-G-T

Variant names:

• chr17-5022672-G-T
• rs146628704
• NM_006612.6:c.2591G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006612.6(KIF1C):​c.2591G>T​(p.Arg864Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R864H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: KIF1C NM_006612.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883
• Publications: 0 publications found

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]

KIF1C-AS1 (HGNC:40324): (KIF1C antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41399378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.2591G>T	p.Arg864Leu	missense_variant	Exon 22 of 23	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.2591G>T	p.Arg864Leu	missense_variant	Exon 23 of 24		XP_005256481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.2591G>T	p.Arg864Leu	missense_variant	Exon 22 of 23	1	NM_006612.6	ENSP00000320821.5
KIF1C-AS1	ENST00000438266.2	n.172-1717C>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422678 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 703610

African (AFR) AF: 0.00 AC: 0 AN: 32640

American (AMR) AF: 0.00 AC: 0 AN: 40622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23546

East Asian (EAS) AF: 0.00 AC: 0 AN: 39246

South Asian (SAS) AF: 0.00 AC: 0 AN: 79686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092732

Other (OTH) AF: 0.00 AC: 0 AN: 58732

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.0000042
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.88
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Polyphen		0.84	P
Vest4		0.64
MutPred		0.28		Loss of MoRF binding (P = 0.0378);
MVP		0.75
MPC		0.97
ClinPred		0.67	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.14
gMVP		0.57
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs146628704; hg19: chr17-4925967;