rs1062465

Variant names:

• chr10-89737874-T-A
• rs1062465
• NM_001284259.2:c.3033T>A

Variant summary

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

The NM_001284259.2(KIF20B):​c.3033T>A​(p.Asp1011Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,612,820 control chromosomes in the GnomAD database, including 59,085 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 0.31 (8164 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50921 hom.)
• Consequence: KIF20B NM_001284259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 26 publications found

Genes affected

KIF20B (HGNC:7212): (kinesin family member 20B) Enables several functions, including WW domain binding activity; plus-end-directed microtubule motor activity; and protein homodimerization activity. Involved in positive regulation of cell population proliferation and positive regulation of cytokinesis. Located in several cellular components, including microtubule cytoskeleton; midbody; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=5.992353E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284259.2. 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
	KIF20B	NM_001284259.2	MANE Select	c.3033T>A	p.Asp1011Glu	missense	Exon 20 of 33	NP_001271188.1
	KIF20B	NM_016195.4		c.2913T>A	p.Asp971Glu	missense	Exon 20 of 33	NP_057279.2
	KIF20B	NM_001382506.1		c.2820T>A	p.Asp940Glu	missense	Exon 19 of 32	NP_001369435.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20B	ENST00000371728.8	TSL:1 MANE Select	c.3033T>A	p.Asp1011Glu	missense	Exon 20 of 33	ENSP00000360793.3
	KIF20B	ENST00000260753.8	TSL:1	c.2913T>A	p.Asp971Glu	missense	Exon 20 of 33	ENSP00000260753.4
	KIF20B	ENST00000478929.1	TSL:1	n.1579T>A		non_coding_transcript_exon	Exon 7 of 20

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46894 AN: 151788 Hom.: 8139 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.282 AC: 70760 AN: 250574 AF XY: 0.289

Gnomad AFR exome AF: 0.465

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.299

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.256 AC: 373786 AN: 1460914 Hom.: 50921 Cov.: 34 AF XY: 0.261 AC XY: 189604 AN XY: 726810

African (AFR) AF: 0.469 AC: 15678 AN: 33444

American (AMR) AF: 0.235 AC: 10499 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 7796 AN: 26106

East Asian (EAS) AF: 0.322 AC: 12750 AN: 39624

South Asian (SAS) AF: 0.437 AC: 37665 AN: 86206

European-Finnish (FIN) AF: 0.249 AC: 13314 AN: 53380

Middle Eastern (MID) AF: 0.237 AC: 1365 AN: 5758

European-Non Finnish (NFE) AF: 0.233 AC: 258611 AN: 1111342

Other (OTH) AF: 0.267 AC: 16108 AN: 60352

GnomAD4 genome AF: 0.309 AC: 46950 AN: 151906 Hom.: 8164 Cov.: 32 AF XY: 0.311 AC XY: 23117 AN XY: 74250

African (AFR) AF: 0.462 AC: 19133 AN: 41454

American (AMR) AF: 0.260 AC: 3970 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1066 AN: 3466

East Asian (EAS) AF: 0.305 AC: 1580 AN: 5188

South Asian (SAS) AF: 0.449 AC: 2160 AN: 4816

European-Finnish (FIN) AF: 0.245 AC: 2581 AN: 10546

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15674 AN: 67846

Other (OTH) AF: 0.271 AC: 571 AN: 2110

Alfa AF: 0.251 Hom.: 3948

Bravo AF: 0.309

TwinsUK AF: 0.236 AC: 876

ALSPAC AF: 0.248 AC: 956

ESP6500AA AF: 0.460 AC: 2027

ESP6500EA AF: 0.233 AC: 2005

ExAC AF: 0.287 AC: 34896

Asia WGS AF: 0.410 AC: 1424 AN: 3474

EpiCase AF: 0.227

EpiControl AF: 0.227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.00060	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.055
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.097
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.22	T
Polyphen		0.76	P
Vest4		0.020
MutPred		0.17		Gain of disorder (P = 0.1961)
MPC		0.027
ClinPred		0.010	T
GERP RS		2.2
Varity_R		0.070
gMVP		0.21
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: rs1062465; hg19: chr10-91497631; COSMIC: COSV53304353;