chr17-5020081-TAGA-T

Variant names:

• chr17-5020081-TAGA-T
• rs551276433
• NM_006612.6:c.1750+6_1750+8delAGA

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_006612.6(KIF1C):​c.1750+6_1750+8delAGA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,583,496 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: KIF1C NM_006612.6 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.68
• 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: Benign. The variant received -12 ACMG points.

• BP6: Variant 17-5020081-TAGA-T is Benign according to our data. Variant chr17-5020081-TAGA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 705102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00101 (154/152196) while in subpopulation AFR AF = 0.00359 (149/41510). AF 95% confidence interval is 0.00312. There are 0 homozygotes in GnomAd4. There are 77 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.1750+6_1750+8delAGA		splice_region intron	N/A	NP_006603.2
	KIF1C-AS1	NR_120665.2		n.10_12delTCT		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.1750+6_1750+8delAGA		splice_region intron	N/A	ENSP00000320821.5	O43896
	KIF1C	ENST00000948910.1		c.1780+6_1780+8delAGA		splice_region intron	N/A	ENSP00000618969.1
	KIF1C	ENST00000948913.1		c.1780+6_1780+8delAGA		splice_region intron	N/A	ENSP00000618972.1

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 156 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000287 AC: 57 AN: 198940 AF XY: 0.000244

Gnomad AFR exome AF: 0.00426

Gnomad AMR exome AF: 0.0000698

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000232

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000122 AC: 174 AN: 1431300 Hom.: 0 AF XY: 0.000116 AC XY: 82 AN XY: 709398

African (AFR) AF: 0.00430 AC: 141 AN: 32806

American (AMR) AF: 0.0000751 AC: 3 AN: 39930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25548

East Asian (EAS) AF: 0.00 AC: 0 AN: 38158

South Asian (SAS) AF: 0.0000244 AC: 2 AN: 81850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51744

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5694

European-Non Finnish (NFE) AF: 0.00000456 AC: 5 AN: 1096240

Other (OTH) AF: 0.000354 AC: 21 AN: 59330

GnomAD4 genome AF: 0.00101 AC: 154 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.00103 AC XY: 77 AN XY: 74404

African (AFR) AF: 0.00359 AC: 149 AN: 41510

American (AMR) AF: 0.000196 AC: 3 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

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

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000434 Hom.: 0

Bravo AF: 0.00117

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	Spastic ataxia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

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: rs551276433; hg19: chr17-4923376;