17-5014050-G-T

Variant names:

• chr17-5014050-G-T
• rs376647
• NM_006612.6:c.1571+318G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006612.6(KIF1C):​c.1571+318G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000555 in 180,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.1571+318G>T		intron_variant	Intron 17 of 22	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.1571+318G>T		intron_variant	Intron 18 of 23		XP_005256481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.1571+318G>T		intron_variant	Intron 17 of 22	1	NM_006612.6	ENSP00000320821.5
KIF1C	ENST00000573815.1	n.-144G>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000555 AC: 1 AN: 180082 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 93152

African (AFR) AF: 0.00 AC: 0 AN: 5532

American (AMR) AF: 0.00 AC: 0 AN: 6792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6120

East Asian (EAS) AF: 0.00 AC: 0 AN: 11096

South Asian (SAS) AF: 0.00 AC: 0 AN: 14274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 934

European-Non Finnish (NFE) AF: 0.00000879 AC: 1 AN: 113706

Other (OTH) AF: 0.00 AC: 0 AN: 11220

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.71
PhyloP100		-0.54

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: rs376647; hg19: chr17-4917345;