rs522496

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-20698408-C-A
• chr1-20698408-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020816.4(KIF17):​c.1204G>T​(p.Val402Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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)
  • Exomes 𝑓: 6.8e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026725382).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF17	NM_001122819.3	MANE Select	c.1204G>T	p.Val402Leu	missense	Exon 6 of 15	NP_001116291.1
	KIF17	NM_020816.4		c.1204G>T	p.Val402Leu	missense	Exon 6 of 15	NP_065867.2
	KIF17	NM_001287212.2		c.904G>T	p.Val302Leu	missense	Exon 6 of 15	NP_001274141.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF17	ENST00000400463.8	TSL:1 MANE Select	c.1204G>T	p.Val402Leu	missense	Exon 6 of 15	ENSP00000383311.3
	KIF17	ENST00000247986.2	TSL:1	c.1204G>T	p.Val402Leu	missense	Exon 6 of 15	ENSP00000247986.2
	KIF17	ENST00000375044.5	TSL:1	c.904G>T	p.Val302Leu	missense	Exon 6 of 15	ENSP00000364184.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461496 Hom.: 0 Cov.: 41 AF XY: 0.00000138 AC XY: 1 AN XY: 727032

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111856

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.1
DANN	Benign	0.73
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.13
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.078
Sift	Benign	0.77	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.030
MutPred		0.16		Gain of catalytic residue at V402 (P = 0.075)
MVP		0.44
MPC		0.14
ClinPred		0.012	T
GERP RS		2.9
Varity_R		0.032
gMVP		0.39
Mutation Taster		=98/2	polymorphism

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;