NM_006612.6:c.1293G>A

Variant names:

• chr17-5007042-G-A
• rs35919356
• NM_006612.6:c.1293G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006612.6(KIF1C):​c.1293G>A​(p.Thr431Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,606,784 control chromosomes in the GnomAD database, including 451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (27 hom., cov: 31)
  • Exomes 𝑓: 0.021 (424 hom.)
• Consequence: KIF1C NM_006612.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.647
• Publications: 4 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 Gene-Disease associations (from GenCC):

• spastic ataxia 2

  Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-5007042-G-A is Benign according to our data. Variant chr17-5007042-G-A is described in ClinVar as Benign. ClinVar VariationId is 380883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.647 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0147 (2245/152216) while in subpopulation NFE AF = 0.0231 (1571/68020). AF 95% confidence interval is 0.0221. There are 27 homozygotes in GnomAd4. There are 1055 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 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.1293G>A	p.Thr431Thr	synonymous	Exon 14 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.1293G>A	p.Thr431Thr	synonymous	Exon 14 of 23	ENSP00000320821.5	O43896
	KIF1C	ENST00000948910.1		c.1323G>A	p.Thr441Thr	synonymous	Exon 14 of 23	ENSP00000618969.1
	KIF1C	ENST00000948913.1		c.1323G>A	p.Thr441Thr	synonymous	Exon 13 of 22	ENSP00000618972.1

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2244 AN: 152098 Hom.: 27 Cov.: 31

Gnomad AFR AF: 0.00372

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0144

GnomAD2 exomes AF: 0.0173 AC: 4137 AN: 239110 AF XY: 0.0178

Gnomad AFR exome AF: 0.00352

Gnomad AMR exome AF: 0.0122

Gnomad ASJ exome AF: 0.00652

Gnomad EAS exome AF: 0.0000572

Gnomad FIN exome AF: 0.0193

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0215 AC: 31273 AN: 1454568 Hom.: 424 Cov.: 32 AF XY: 0.0213 AC XY: 15406 AN XY: 723796

African (AFR) AF: 0.00290 AC: 95 AN: 32718

American (AMR) AF: 0.0108 AC: 454 AN: 42174

Ashkenazi Jewish (ASJ) AF: 0.00665 AC: 172 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.0143 AC: 1216 AN: 85278

European-Finnish (FIN) AF: 0.0210 AC: 1120 AN: 53324

Middle Eastern (MID) AF: 0.0140 AC: 80 AN: 5728

European-Non Finnish (NFE) AF: 0.0244 AC: 27039 AN: 1109814

Other (OTH) AF: 0.0183 AC: 1097 AN: 60038

GnomAD4 genome AF: 0.0147 AC: 2245 AN: 152216 Hom.: 27 Cov.: 31 AF XY: 0.0142 AC XY: 1055 AN XY: 74414

African (AFR) AF: 0.00371 AC: 154 AN: 41532

American (AMR) AF: 0.0100 AC: 153 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4820

European-Finnish (FIN) AF: 0.0174 AC: 184 AN: 10600

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0231 AC: 1571 AN: 68020

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

Alfa AF: 0.0178 Hom.: 21

Bravo AF: 0.0136

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.0214

EpiControl AF: 0.0198

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Spastic ataxia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.17
PhyloP100		-0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs35919356; hg19: chr17-4910337;