rs13375609

Positions:

• chr1-20684837-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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. 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.010 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (24 hom.)
• Consequence: KIF17 NM_001122819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

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=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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF17	NM_001122819.3	c.2203G>A	p.Val735Ile	missense_variant	10/15	ENST00000400463.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF17	ENST00000400463.8	c.2203G>A	p.Val735Ile	missense_variant	10/15	1	NM_001122819.3	A2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1531 AN: 152166 Hom.: 20 Cov.: 33

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

GnomAD3 exomes AF: 0.00243 AC: 520 AN: 214036 Hom.: 8 AF XY: 0.00180 AC XY: 208 AN XY: 115614

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 SAS exome AF: 0.000113

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.: 24 Cov.: 32 AF XY: 0.00110 AC XY: 786 AN XY: 713604

Gnomad4 AFR exome AF: 0.0354

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000197

Gnomad4 OTH exome AF: 0.00348

GnomAD4 genome AF: 0.0101 AC: 1533 AN: 152284 Hom.: 20 Cov.: 33 AF XY: 0.00955 AC XY: 711 AN XY: 74454

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00251 Hom.: 11

Bravo AF: 0.0119

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0353 AC: 155

ESP6500EA AF: 0.000816 AC: 7

ExAC AF: 0.00254 AC: 307

Asia WGS AF: 0.00202 AC: 7 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	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0030
DANN	Benign	0.65
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.49	T;T;T
MetaRNN	Benign	0.0023	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
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	T
GERP RS		-8.7
Varity_R		0.012
gMVP		0.078

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: rs13375609; hg19: chr1-21011330;