chr1-20666326-G-C

Position:

• chr1-20666326-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122819.3(KIF17):​c.2796C>G​(p.Asp932Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,611,810 control chromosomes in the GnomAD database, including 495,918 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.77 (45583 hom., cov: 33)
  • Exomes 𝑓: 0.78 (450335 hom.)
• Consequence: KIF17 NM_001122819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.315123E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF17	NM_001122819.3	c.2796C>G	p.Asp932Glu	missense_variant	14/15	ENST00000400463.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF17	ENST00000400463.8	c.2796C>G	p.Asp932Glu	missense_variant	14/15	1	NM_001122819.3	A2

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117338 AN: 152050 Hom.: 45538 Cov.: 33

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.798

GnomAD3 exomes AF: 0.752 AC: 189019 AN: 251462 Hom.: 72006 AF XY: 0.751 AC XY: 102132 AN XY: 135906

Gnomad AFR exome AF: 0.762

Gnomad AMR exome AF: 0.701

Gnomad ASJ exome AF: 0.847

Gnomad EAS exome AF: 0.552

Gnomad SAS exome AF: 0.665

Gnomad FIN exome AF: 0.803

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.783

GnomAD4 exome AF: 0.783 AC: 1142658 AN: 1459642 Hom.: 450335 Cov.: 36 AF XY: 0.780 AC XY: 566219 AN XY: 726238

Gnomad4 AFR exome AF: 0.753

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.843

Gnomad4 EAS exome AF: 0.538

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.797

Gnomad4 NFE exome AF: 0.803

Gnomad4 OTH exome AF: 0.777

GnomAD4 genome AF: 0.772 AC: 117436 AN: 152168 Hom.: 45583 Cov.: 33 AF XY: 0.769 AC XY: 57214 AN XY: 74396

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.800

Alfa AF: 0.791 Hom.: 32735

Bravo AF: 0.768

TwinsUK AF: 0.812 AC: 3012

ALSPAC AF: 0.794 AC: 3062

ESP6500AA AF: 0.761 AC: 3352

ESP6500EA AF: 0.805 AC: 6926

ExAC AF: 0.752 AC: 91311

Asia WGS AF: 0.616 AC: 2145 AN: 3478

EpiCase AF: 0.814

EpiControl AF: 0.809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.2
DANN	Benign	0.53
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.23	T;T;T
MetaRNN	Benign	6.3e-7	T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.59	N;N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.067
MutPred		0.10		.;.;Gain of MoRF binding (P = 0.273);
MPC		0.39
ClinPred		0.00015	T
GERP RS		3.7
Varity_R		0.039
gMVP		0.096

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs631357; hg19: chr1-20992819; COSMIC: COSV56121685; COSMIC: COSV56121685;