Variant 1-20664705-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001122819.3(KIF17):c.2966C>T(p.Pro989Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KIF17
NM_001122819.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.257

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:

KIF17 (HGNC:):

KIF17 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052214146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF17	NM_001122819.3 linkuse as main transcript	c.2966C>T	p.Pro989Leu	missense_variant	15/15	ENST00000400463.8	NP_001116291.1	Q9P2E2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF17	ENST00000400463.8 linkuse as main transcript	c.2966C>T	p.Pro989Leu	missense_variant	15/15	1	NM_001122819.3	ENSP00000383311.3		Q9P2E2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1456258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724638

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:

0.00

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 01, 2024

The c.2969C>T (p.P990L) alteration is located in exon 15 (coding exon 15) of the KIF17 gene. This alteration results from a C to T substitution at nucleotide position 2969, causing the proline (P) at amino acid position 990 to be replaced by a leucine (L). 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

Benign

0.064

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.0

DANN

Benign

0.77

DEOGEN2

Benign

0.0095

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

.;.;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.10

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.83

T;T;T

Polyphen

0.0030, 0.0020

.;B;B

Vest4

0.090

MutPred

0.37

.;.;Loss of glycosylation at S987 (P = 0.0548);

MVP

0.57

MPC

0.43

ClinPred

0.11

GERP RS

2.3

Varity_R

0.042

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over