1-20698408-C-T

Variant names:

• chr1-20698408-C-T
• rs522496
• NM_001122819.3:c.1204G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020816.4(KIF17):​c.1204G>A​(p.Val402Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,612,652 control chromosomes in the GnomAD database, including 317,327 homozygotes. 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: 𝑓 0.60 (27543 hom., cov: 32)
  • Exomes 𝑓: 0.63 (289784 hom.)
• Consequence: KIF17 NM_020816.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 30 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.1858882E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020816.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF17	NM_001122819.3	MANE Select	c.1204G>A	p.Val402Met	missense	Exon 6 of 15	NP_001116291.1
	KIF17	NM_020816.4		c.1204G>A	p.Val402Met	missense	Exon 6 of 15	NP_065867.2
	KIF17	NM_001287212.2		c.904G>A	p.Val302Met	missense	Exon 6 of 15	NP_001274141.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF17	ENST00000400463.8	TSL:1 MANE Select	c.1204G>A	p.Val402Met	missense	Exon 6 of 15	ENSP00000383311.3
	KIF17	ENST00000247986.2	TSL:1	c.1204G>A	p.Val402Met	missense	Exon 6 of 15	ENSP00000247986.2
	KIF17	ENST00000375044.5	TSL:1	c.904G>A	p.Val302Met	missense	Exon 6 of 15	ENSP00000364184.1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90829 AN: 151892 Hom.: 27521 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.596

GnomAD2 exomes AF: 0.628 AC: 157356 AN: 250520 AF XY: 0.627

Gnomad AFR exome AF: 0.490

Gnomad AMR exome AF: 0.664

Gnomad ASJ exome AF: 0.688

Gnomad EAS exome AF: 0.631

Gnomad FIN exome AF: 0.681

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.630

GnomAD4 exome AF: 0.629 AC: 918494 AN: 1460640 Hom.: 289784 Cov.: 41 AF XY: 0.627 AC XY: 455422 AN XY: 726658

African (AFR) AF: 0.476 AC: 15915 AN: 33456

American (AMR) AF: 0.662 AC: 29606 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 18047 AN: 26126

East Asian (EAS) AF: 0.631 AC: 25043 AN: 39692

South Asian (SAS) AF: 0.572 AC: 49366 AN: 86232

European-Finnish (FIN) AF: 0.674 AC: 35850 AN: 53180

Middle Eastern (MID) AF: 0.637 AC: 3668 AN: 5762

European-Non Finnish (NFE) AF: 0.633 AC: 703082 AN: 1111126

Other (OTH) AF: 0.628 AC: 37917 AN: 60354

GnomAD4 genome AF: 0.598 AC: 90903 AN: 152012 Hom.: 27543 Cov.: 32 AF XY: 0.599 AC XY: 44522 AN XY: 74284

African (AFR) AF: 0.486 AC: 20139 AN: 41438

American (AMR) AF: 0.658 AC: 10047 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2432 AN: 3470

East Asian (EAS) AF: 0.630 AC: 3246 AN: 5152

South Asian (SAS) AF: 0.578 AC: 2788 AN: 4820

European-Finnish (FIN) AF: 0.670 AC: 7078 AN: 10568

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43313 AN: 67978

Other (OTH) AF: 0.595 AC: 1255 AN: 2108

Alfa AF: 0.623 Hom.: 96448

Bravo AF: 0.590

TwinsUK AF: 0.635 AC: 2355

ALSPAC AF: 0.633 AC: 2440

ESP6500AA AF: 0.498 AC: 2196

ESP6500EA AF: 0.639 AC: 5496

ExAC AF: 0.620 AC: 75289

Asia WGS AF: 0.598 AC: 2081 AN: 3478

EpiCase AF: 0.637

EpiControl AF: 0.648

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.1
DANN	Benign	0.70
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.069	T
MetaRNN	Benign	0.0000022	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.13
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.047
Sift	Benign	0.79	T
Sift4G	Benign	0.29	T
Polyphen		0.0060	B
Vest4		0.021
MPC		0.15
ClinPred		0.0042	T
GERP RS		2.9
Varity_R		0.026
gMVP		0.34
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs522496; hg19: chr1-21024901; COSMIC: COSV56116051; COSMIC: COSV56116051;