1-20666326-G-C

Variant names:

• chr1-20666326-G-C
• rs631357
• NM_001122819.3:c.2796C>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.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. 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 0.77 (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
• Publications: 27 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=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 rank	MANE	Protein	UniProt
KIF17	NM_001122819.3	c.2796C>G	p.Asp932Glu	missense_variant	Exon 14 of 15	ENST00000400463.8	NP_001116291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF17	ENST00000400463.8	c.2796C>G	p.Asp932Glu	missense_variant	Exon 14 of 15	1	NM_001122819.3	ENSP00000383311.3

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

GnomAD2 exomes AF: 0.752 AC: 189019 AN: 251462 AF XY: 0.751

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 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

African (AFR) AF: 0.753 AC: 25182 AN: 33440

American (AMR) AF: 0.705 AC: 31505 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 22010 AN: 26118

East Asian (EAS) AF: 0.538 AC: 21355 AN: 39700

South Asian (SAS) AF: 0.663 AC: 57206 AN: 86222

European-Finnish (FIN) AF: 0.797 AC: 42549 AN: 53396

Middle Eastern (MID) AF: 0.870 AC: 5012 AN: 5762

European-Non Finnish (NFE) AF: 0.803 AC: 890951 AN: 1109962

Other (OTH) AF: 0.777 AC: 46888 AN: 60324

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

African (AFR) AF: 0.760 AC: 31530 AN: 41514

American (AMR) AF: 0.736 AC: 11251 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2932 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2795 AN: 5152

South Asian (SAS) AF: 0.654 AC: 3157 AN: 4824

European-Finnish (FIN) AF: 0.806 AC: 8538 AN: 10598

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54558 AN: 67996

Other (OTH) AF: 0.800 AC: 1691 AN: 2114

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
DEOGEN2	Benign	0.0098	.;.;T
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
MutationAssessor	Benign	-1.7	.;.;N
PhyloP100		0.99
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs631357; hg19: chr1-20992819; COSMIC: COSV56121685; COSMIC: COSV56121685;