Genetic Variant NM_001122819.3:c.2203G>A (chr1-20684837-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001122819.3(KIF17):c.2203G>A(p.Val735Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,590,884 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.010 ( 20 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 24 hom. )

Consequence

KIF17
NM_001122819.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.55

Publications

7 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:

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 (MetaRNN=0.002274394).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1533/152284) while in subpopulation AFR AF = 0.0339 (1408/41536). AF 95% confidence interval is 0.0324. There are 20 homozygotes in GnomAd4. There are 711 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF17	NM_001122819.3 link	c.2203G>A	p.Val735Ile	missense_variant	Exon 10 of 15	ENST00000400463.8	NP_001116291.1	Q9P2E2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF17	ENST00000400463.8 link	c.2203G>A	p.Val735Ile	missense_variant	Exon 10 of 15	1	NM_001122819.3	ENSP00000383311.3		Q9P2E2-3

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1531

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00243

AC:

520

AN:

214036

AF XY:

0.00180

show subpopulations

Gnomad AFR exome

AF:

0.0319

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000391

Gnomad OTH exome

AF:

0.00204

GnomAD4 exome

AF:

0.00120

AC:

1729

AN:

1438600

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

786

AN XY:

713604

show subpopulations

African (AFR)

AF:

0.0354

AC:

1164

AN:

32892

American (AMR)

AF:

0.00268

AC:

112

AN:

41802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25552

East Asian (EAS)

AF:

0.00

AC:

AN:

38246

South Asian (SAS)

AF:

0.000121

AC:

AN:

82766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51544

Middle Eastern (MID)

AF:

0.00357

AC:

AN:

5324

European-Non Finnish (NFE)

AF:

0.000197

AC:

217

AN:

1101052

Other (OTH)

AF:

0.00348

AC:

207

AN:

59422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

102

203

305

406

508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0101

AC:

1533

AN:

152284

Hom.:

Cov.:

AF XY:

0.00955

AC XY:

711

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0339

AC:

1408

AN:

41536

American (AMR)

AF:

0.00542

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68022

Other (OTH)

AF:

0.0114

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

145

217

290

362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00427

Hom.:

Bravo

AF:

0.0119

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0353

AC:

155

ESP6500EA

AF:

0.000816

AC:

ExAC

AF:

0.00254

AC:

307

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.0030

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.020

.;.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.49

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;N

PhyloP100

-3.5

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.16

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.59

T;T;T

Sift4G

Benign

0.60

T;T;T

Polyphen

0.0010, 0.0

.;B;B

Vest4

0.038

MVP

0.42

MPC

0.12

ClinPred

0.0051

GERP RS

-8.7

Varity_R

0.012

gMVP

0.078

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over