rs57144955

Variant names:

• chr17-5014827-A-G
• rs57144955
• NM_006612.6:c.1656A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006612.6(KIF1C):​c.1656A>G​(p.Pro552Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 1,591,798 control chromosomes in the GnomAD database, including 593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (303 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (290 hom.)
• Consequence: KIF1C NM_006612.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.81
• Publications: 1 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=-0.87).
• BP6: Variant 17-5014827-A-G is Benign according to our data. Variant chr17-5014827-A-G is described in ClinVar as Benign. ClinVar VariationId is 387793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

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.1656A>G	p.Pro552Pro	synonymous	Exon 18 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.1656A>G	p.Pro552Pro	synonymous	Exon 18 of 23	ENSP00000320821.5	O43896
	KIF1C	ENST00000948910.1		c.1686A>G	p.Pro562Pro	synonymous	Exon 18 of 23	ENSP00000618969.1
	KIF1C	ENST00000948913.1		c.1686A>G	p.Pro562Pro	synonymous	Exon 17 of 22	ENSP00000618972.1

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5300 AN: 152156 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.00875 AC: 1859 AN: 212502 AF XY: 0.00606

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.00818

Gnomad ASJ exome AF: 0.000436

Gnomad EAS exome AF: 0.0000615

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000454

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00373 AC: 5376 AN: 1439524 Hom.: 290 Cov.: 30 AF XY: 0.00325 AC XY: 2318 AN XY: 713444

African (AFR) AF: 0.124 AC: 4120 AN: 33246

American (AMR) AF: 0.00881 AC: 359 AN: 40772

Ashkenazi Jewish (ASJ) AF: 0.000705 AC: 18 AN: 25542

East Asian (EAS) AF: 0.00 AC: 0 AN: 39124

South Asian (SAS) AF: 0.000365 AC: 30 AN: 82200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51824

Middle Eastern (MID) AF: 0.00782 AC: 45 AN: 5754

European-Non Finnish (NFE) AF: 0.000254 AC: 280 AN: 1101348

Other (OTH) AF: 0.00878 AC: 524 AN: 59714

GnomAD4 genome AF: 0.0349 AC: 5309 AN: 152274 Hom.: 303 Cov.: 32 AF XY: 0.0328 AC XY: 2442 AN XY: 74460

African (AFR) AF: 0.119 AC: 4926 AN: 41536

American (AMR) AF: 0.0191 AC: 293 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

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

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68018

Other (OTH) AF: 0.0241 AC: 51 AN: 2116

Alfa AF: 0.0161 Hom.: 71

Bravo AF: 0.0402

Asia WGS AF: 0.00693 AC: 26 AN: 3478

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	-0.87
CADD	Benign	2.4
DANN	Benign	0.65
PhyloP100		-1.8
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: rs57144955; hg19: chr17-4918122;