NM_006612.6:c.-149+531C>T

Variant names:

• chr17-4998687-C-T
• rs11658587
• NM_006612.6:c.-149+531C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_006612.6(KIF1C):​c.-149+531C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 152,328 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.021 (53 hom., cov: 33)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 6 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]

INCA1 (HGNC:32224): (inhibitor of CDK, cyclin A1 interacting protein 1) Enables cyclin binding activity; cyclin-dependent protein serine/threonine kinase inhibitor activity; and identical protein binding activity. Acts upstream of or within negative regulation of cyclin-dependent protein serine/threonine kinase activity. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0206 (3136/152328) while in subpopulation NFE AF = 0.0332 (2261/68010). AF 95% confidence interval is 0.0321. There are 53 homozygotes in GnomAd4. There are 1421 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 AR,AD gene

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.-149+531C>T		intron	N/A	NP_006603.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.-149+531C>T		intron	N/A	ENSP00000320821.5
	KIF1C	ENST00000894747.1		c.-508C>T		5_prime_UTR	Exon 1 of 23	ENSP00000564806.1
	KIF1C	ENST00000919365.1		c.-1311C>T		5_prime_UTR	Exon 1 of 22	ENSP00000589424.1

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3137 AN: 152210 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.00523

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0206 AC: 3136 AN: 152328 Hom.: 53 Cov.: 33 AF XY: 0.0191 AC XY: 1421 AN XY: 74498

African (AFR) AF: 0.00522 AC: 217 AN: 41588

American (AMR) AF: 0.0231 AC: 354 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4832

European-Finnish (FIN) AF: 0.0153 AC: 162 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0332 AC: 2261 AN: 68010

Other (OTH) AF: 0.0227 AC: 48 AN: 2110

Alfa AF: 0.0268 Hom.: 109

Bravo AF: 0.0204

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.84
PhyloP100		1.3
Mutation Taster		=100/0	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: rs11658587; hg19: chr17-4901982;