Genetic Variant NM_001122819.3:c.1021A>C (chr1-20704549-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001122819.3(KIF17):c.1021A>C(p.Ile341Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KIF17
NM_001122819.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.49

Publications

25 publications found

Variant links:

Genes affected

KIF17 (HGNC:19167): (kinesin family member 17) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in anterograde dendritic transport of neurotransmitter receptor complex and cell projection organization. Predicted to act upstream of or within microtubule-based process; protein-containing complex localization; and vesicle-mediated transport. Predicted to be located in microtubule cytoskeleton. Predicted to be part of intraciliary transport particle B and kinesin complex. Predicted to be active in cilium; microtubule cytoskeleton; and neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

KIF17 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

KIF17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122819.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIF17	NM_001122819.3	MANE Select	c.1021A>C	p.Ile341Leu	missense	Exon 5 of 15	NP_001116291.1
KIF17	NM_020816.4		c.1021A>C	p.Ile341Leu	missense	Exon 5 of 15	NP_065867.2
KIF17	NM_001287212.2		c.721A>C	p.Ile241Leu	missense	Exon 5 of 15	NP_001274141.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIF17	ENST00000400463.8	TSL:1 MANE Select	c.1021A>C	p.Ile341Leu	missense	Exon 5 of 15	ENSP00000383311.3
KIF17	ENST00000247986.2	TSL:1	c.1021A>C	p.Ile341Leu	missense	Exon 5 of 15	ENSP00000247986.2
KIF17	ENST00000375044.5	TSL:1	c.721A>C	p.Ile241Leu	missense	Exon 5 of 15	ENSP00000364184.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251444

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

0.13

MutationAssessor

Pathogenic

3.8

PhyloP100

1.5

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.010

Polyphen

0.86

Vest4

0.55

MutPred

0.20

Gain of loop (P = 0.1081)

MVP

0.85

MPC

0.29

ClinPred

0.95

GERP RS

5.3

Varity_R

0.19

gMVP

0.30

Mutation Taster

=80/20

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over