17-5000100-T-C

Position:

• chr17-5000100-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006612.6(KIF1C):​c.-27-120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 628,466 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (138 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (45 hom.)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.301

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-5000100-T-C is Benign according to our data. Variant chr17-5000100-T-C is described in ClinVar as [Benign]. Clinvar id is 1238133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.-27-120T>C		intron_variant		ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.-27-120T>C		intron_variant			XP_005256481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.-27-120T>C		intron_variant		1	NM_006612.6	ENSP00000320821.5
KIF1C	ENST00000574165.1	c.-27-120T>C		intron_variant		5		ENSP00000458697.1

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3571 AN: 152178 Hom.: 138 Cov.: 33

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00877

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.00301 AC: 1435 AN: 476170 Hom.: 45 Cov.: 5 AF XY: 0.00246 AC XY: 619 AN XY: 251558

Gnomad4 AFR exome AF: 0.0807

Gnomad4 AMR exome AF: 0.00623

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000207

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000964

Gnomad4 OTH exome AF: 0.00693

GnomAD4 genome AF: 0.0235 AC: 3576 AN: 152296 Hom.: 138 Cov.: 33 AF XY: 0.0224 AC XY: 1671 AN XY: 74462

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.00876

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0167 Hom.: 6

Bravo AF: 0.0260

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.0
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs75284304; hg19: chr17-4903395;