17-5023901-C-T

Variant names:

• chr17-5023901-C-T
• rs369620316
• NM_006612.6:c.3062C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006612.6(KIF1C):​c.3062C>T​(p.Pro1021Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,551,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P1021P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: KIF1C NM_006612.6 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.41
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19308954).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006612.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	NM_006612.6	MANE Select	c.3062C>T	p.Pro1021Leu	missense	Exon 23 of 23	NP_006603.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.3062C>T	p.Pro1021Leu	missense	Exon 23 of 23	ENSP00000320821.5	O43896
	KIF1C	ENST00000948910.1		c.3092C>T	p.Pro1031Leu	missense	Exon 23 of 23	ENSP00000618969.1
	KIF1C	ENST00000948913.1		c.3092C>T	p.Pro1031Leu	missense	Exon 22 of 22	ENSP00000618972.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000202 AC: 4 AN: 198490 AF XY: 0.0000282

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000764

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000221

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000193 AC: 27 AN: 1399636 Hom.: 0 Cov.: 35 AF XY: 0.0000232 AC XY: 16 AN XY: 690110

African (AFR) AF: 0.00 AC: 0 AN: 31396

American (AMR) AF: 0.0000564 AC: 2 AN: 35432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21786

East Asian (EAS) AF: 0.00 AC: 0 AN: 38916

South Asian (SAS) AF: 0.00 AC: 0 AN: 77136

European-Finnish (FIN) AF: 0.0000585 AC: 3 AN: 51254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 0.0000185 AC: 20 AN: 1080742

Other (OTH) AF: 0.0000348 AC: 2 AN: 57524

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	Spastic ataxia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.89	P
Vest4		0.13
MVP		0.73
MPC		0.86
ClinPred		0.29	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.052
gMVP		0.42
Mutation Taster		=98/2	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: rs369620316; hg19: chr17-4927196; COSMIC: COSV57905675; COSMIC: COSV57905675;