Variant 1-20682787-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001122819.3(KIF17):c.2329C>G(p.Arg777Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R777H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KIF17
NM_001122819.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.802

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF17	NM_001122819.3 linkuse as main transcript	c.2329C>G	p.Arg777Gly	missense_variant	11/15	ENST00000400463.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF17	ENST00000400463.8 linkuse as main transcript	c.2329C>G	p.Arg777Gly	missense_variant	11/15	1	NM_001122819.3	A2	Q9P2E2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460434

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2021

The c.2329C>G (p.R777G) alteration is located in exon 11 (coding exon 11) of the KIF17 gene. This alteration results from a C to G substitution at nucleotide position 2329, causing the arginine (R) at amino acid position 777 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Uncertain

0.32

MutationTaster

Benign

0.61

D;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.2

D;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0, 0.44

.;D;B

Vest4

0.80

MutPred

0.52

.;Loss of stability (P = 0.0273);Loss of stability (P = 0.0273);

MVP

0.88

MPC

0.73

ClinPred

0.99

GERP RS

5.8

Varity_R

0.41

gMVP

0.56

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over