Genetic Variant NM_006612.6:c.1571+318G>C (chr17-5014050-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006612.6(KIF1C):c.1571+318G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 332,192 control chromosomes in the GnomAD database, including 766 homozygotes. 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: 𝑓 0.048 ( 237 hom., cov: 32)

Exomes 𝑓: 0.061 ( 529 hom. )

Consequence

KIF1C
NM_006612.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.539

Publications

1 publications found

Variant links:

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

KIF1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6 link	c.1571+318G>C		intron_variant	Intron 17 of 22	ENST00000320785.10	NP_006603.2	O43896
KIF1C	XM_005256424.3 link	c.1571+318G>C		intron_variant	Intron 18 of 23		XP_005256481.1	O43896

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10 link	c.1571+318G>C		intron_variant	Intron 17 of 22	1	NM_006612.6	ENSP00000320821.5		O43896
KIF1C	ENST00000573815.1 link	n.-144G>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0480

AC:

7298

AN:

152172

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0367

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0413

Gnomad ASJ

AF:

0.0536

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.0992

Gnomad FIN

AF:

0.0254

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0449

Gnomad OTH

AF:

0.0516

GnomAD4 exome

AF:

0.0607

AC:

10920

AN:

179902

Hom.:

529

AF XY:

0.0618

AC XY:

5749

AN XY:

93054

show subpopulations

African (AFR)

AF:

0.0389

AC:

215

AN:

5528

American (AMR)

AF:

0.0402

AC:

273

AN:

6786

Ashkenazi Jewish (ASJ)

AF:

0.0685

AC:

419

AN:

6118

East Asian (EAS)

AF:

0.230

AC:

2540

AN:

11052

South Asian (SAS)

AF:

0.0869

AC:

1238

AN:

14248

European-Finnish (FIN)

AF:

0.0316

AC:

329

AN:

10402

Middle Eastern (MID)

AF:

0.0783

AC:

AN:

932

European-Non Finnish (NFE)

AF:

0.0459

AC:

5214

AN:

113628

Other (OTH)

AF:

0.0552

AC:

619

AN:

11208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

483

967

1450

1934

2417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0479

AC:

7291

AN:

152290

Hom.:

237

Cov.:

AF XY:

0.0490

AC XY:

3647

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0367

AC:

1524

AN:

41556

American (AMR)

AF:

0.0413

AC:

632

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0536

AC:

186

AN:

3472

East Asian (EAS)

AF:

0.199

AC:

1032

AN:

5176

South Asian (SAS)

AF:

0.0980

AC:

473

AN:

4826

European-Finnish (FIN)

AF:

0.0254

AC:

270

AN:

10624

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0449

AC:

3053

AN:

68018

Other (OTH)

AF:

0.0501

AC:

106

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

375

749

1124

1498

1873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0463

Hom.:

Bravo

AF:

0.0490

Asia WGS

AF:

0.127

AC:

442

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.12

(source)

DANN

Benign

0.54

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over