Genetic Variant KIF20B:p.Asn1219Ser (chr10-89738497-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001284259.2(KIF20B):c.3656A>G(p.Asn1219Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,604,082 control chromosomes in the GnomAD database, including 58,824 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 ( 8382 hom., cov: 33)

Exomes 𝑓: 0.25 ( 50442 hom. )

Consequence

KIF20B
NM_001284259.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.142

Publications

32 publications found

Variant links:

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]

KIF20B links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=6.440282E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF20B	NM_001284259.2 link	c.3656A>G	p.Asn1219Ser	missense_variant	Exon 20 of 33	ENST00000371728.8	NP_001271188.1	Q96Q89-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIF20B	ENST00000371728.8 link	c.3656A>G	p.Asn1219Ser	missense_variant	Exon 20 of 33	1	NM_001284259.2	ENSP00000360793.3	Q96Q89-1
KIF20B	ENST00000260753.8 link	c.3536A>G	p.Asn1179Ser	missense_variant	Exon 20 of 33	1		ENSP00000260753.4	Q96Q89-3
KIF20B	ENST00000478929.1 link	n.2202A>G		non_coding_transcript_exon_variant	Exon 7 of 20	1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47364

AN:

151846

Hom.:

8355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.263

GnomAD2 exomes

AF:

0.281

AC:

68733

AN:

244886

AF XY:

0.286

show subpopulations

Gnomad AFR exome

AF:

0.475

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.251

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.255

AC:

370192

AN:

1452116

Hom.:

50442

Cov.:

AF XY:

0.260

AC XY:

187667

AN XY:

722122

show subpopulations

African (AFR)

AF:

0.477

AC:

15739

AN:

32968

American (AMR)

AF:

0.233

AC:

10175

AN:

43662

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

7718

AN:

25906

East Asian (EAS)

AF:

0.322

AC:

12705

AN:

39502

South Asian (SAS)

AF:

0.436

AC:

36534

AN:

83836

European-Finnish (FIN)

AF:

0.249

AC:

13299

AN:

53334

Middle Eastern (MID)

AF:

0.236

AC:

1355

AN:

5730

European-Non Finnish (NFE)

AF:

0.232

AC:

256691

AN:

1107170

Other (OTH)

AF:

0.266

AC:

15976

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

12705

25409

38114

50818

63523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9130

18260

27390

36520

45650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.312

AC:

47422

AN:

151966

Hom.:

8382

Cov.:

AF XY:

0.314

AC XY:

23295

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.472

AC:

19578

AN:

41492

American (AMR)

AF:

0.261

AC:

3993

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1066

AN:

3466

East Asian (EAS)

AF:

0.304

AC:

1573

AN:

5176

South Asian (SAS)

AF:

0.449

AC:

2164

AN:

4820

European-Finnish (FIN)

AF:

0.244

AC:

2579

AN:

10554

Middle Eastern (MID)

AF:

0.233

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.231

AC:

15682

AN:

67862

Other (OTH)

AF:

0.271

AC:

572

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1589

3179

4768

6358

7947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.258

Hom.:

19506

Bravo

AF:

0.311

TwinsUK

AF:

0.236

AC:

875

ALSPAC

AF:

0.248

AC:

957

ESP6500AA

AF:

0.455

AC:

1966

ESP6500EA

AF:

0.230

AC:

1972

ExAC

AF:

0.288

AC:

34860

Asia WGS

AF:

0.411

AC:

1426

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.8

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.0062

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.00064

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.6

.;N

PhyloP100

0.14

PrimateAI

Benign

0.31

PROVEAN

Benign

0.54

N;N

REVEL

Benign

0.095

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.027

MPC

0.018

ClinPred

0.0041

GERP RS

-0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.054

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over