chr1-20666234-G-A

Position:

• chr1-20666234-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001122819.3(KIF17):​c.2888C>T​(p.Thr963Ile) 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. 14/21 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: 32)
• Consequence: KIF17 NM_001122819.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14802542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF17	NM_001122819.3	c.2888C>T	p.Thr963Ile	missense_variant	14/15	ENST00000400463.8	NP_001116291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF17	ENST00000400463.8	c.2888C>T	p.Thr963Ile	missense_variant	14/15	1	NM_001122819.3	ENSP00000383311.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.2891C>T (p.T964I) alteration is located in exon 14 (coding exon 14) of the KIF17 gene. This alteration results from a C to T substitution at nucleotide position 2891, causing the threonine (T) at amino acid position 964 to be replaced by an isoleucine (I). 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	0.20
BayesDel_addAF	Benign	-0.0014	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	.;.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.042	D;D;D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		0.47, 0.34	.;P;B
Vest4		0.25
MutPred		0.29		.;.;Loss of glycosylation at S963 (P = 0.0701);
MVP		0.74
MPC		0.66
ClinPred		0.47	T
GERP RS		5.0
Varity_R		0.054
gMVP		0.24

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

Other links and lift over

dbSNP: rs769629585; hg19: chr1-20992727;