rs2296225

Variant names:

• chr1-20704549-T-C
• rs2296225
• NM_001122819.3:c.1021A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-20704549-T-C
• chr1-20704549-T-G

Variant summary

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

The NM_001122819.3(KIF17):​c.1021A>G​(p.Ile341Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 1,614,136 control chromosomes in the GnomAD database, including 10,393 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.098 (977 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9416 hom.)
• Consequence: KIF17 NM_001122819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 25 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=0.0017932355).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF17	NM_001122819.3	c.1021A>G	p.Ile341Val	missense_variant	Exon 5 of 15	ENST00000400463.8	NP_001116291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF17	ENST00000400463.8	c.1021A>G	p.Ile341Val	missense_variant	Exon 5 of 15	1	NM_001122819.3	ENSP00000383311.3
KIF17	ENST00000247986.2	c.1021A>G	p.Ile341Val	missense_variant	Exon 5 of 15	1		ENSP00000247986.2
KIF17	ENST00000375044.5	c.721A>G	p.Ile241Val	missense_variant	Exon 5 of 15	1		ENSP00000364184.1

Frequencies

GnomAD3 genomes AF: 0.0982 AC: 14944 AN: 152136 Hom.: 982 Cov.: 32

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.118 AC: 29594 AN: 251444 AF XY: 0.123

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.0866

Gnomad ASJ exome AF: 0.0543

Gnomad EAS exome AF: 0.320

Gnomad FIN exome AF: 0.0410

Gnomad NFE exome AF: 0.0834

Gnomad OTH exome AF: 0.0974

GnomAD4 exome AF: 0.0997 AC: 145801 AN: 1461882 Hom.: 9416 Cov.: 35 AF XY: 0.104 AC XY: 75720 AN XY: 727244

African (AFR) AF: 0.0990 AC: 3316 AN: 33480

American (AMR) AF: 0.0846 AC: 3782 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0561 AC: 1467 AN: 26136

East Asian (EAS) AF: 0.289 AC: 11489 AN: 39700

South Asian (SAS) AF: 0.242 AC: 20859 AN: 86256

European-Finnish (FIN) AF: 0.0430 AC: 2297 AN: 53420

Middle Eastern (MID) AF: 0.0993 AC: 573 AN: 5768

European-Non Finnish (NFE) AF: 0.0860 AC: 95606 AN: 1112002

Other (OTH) AF: 0.106 AC: 6412 AN: 60396

GnomAD4 genome AF: 0.0981 AC: 14934 AN: 152254 Hom.: 977 Cov.: 32 AF XY: 0.101 AC XY: 7490 AN XY: 74450

African (AFR) AF: 0.0985 AC: 4095 AN: 41562

American (AMR) AF: 0.0757 AC: 1158 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1598 AN: 5160

South Asian (SAS) AF: 0.252 AC: 1218 AN: 4824

European-Finnish (FIN) AF: 0.0425 AC: 451 AN: 10622

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0847 AC: 5758 AN: 67996

Other (OTH) AF: 0.105 AC: 223 AN: 2114

Alfa AF: 0.0915 Hom.: 2543

Bravo AF: 0.100

TwinsUK AF: 0.0895 AC: 332

ALSPAC AF: 0.0916 AC: 353

ESP6500AA AF: 0.0971 AC: 428

ESP6500EA AF: 0.0837 AC: 720

ExAC AF: 0.120 AC: 14585

Asia WGS AF: 0.235 AC: 819 AN: 3478

EpiCase AF: 0.0918

EpiControl AF: 0.0852

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	.;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.0013
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	D;T;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	.;M;M
PhyloP100		1.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.83	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.084, 0.050	.;B;B
Vest4		0.17
MPC		0.13
ClinPred		0.0094	T
GERP RS		5.3
Varity_R		0.051
gMVP		0.24
Mutation Taster		=89/11	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: rs2296225; hg19: chr1-21031042; COSMIC: COSV56120839;