Genetic Variant NM_001284259.2:c.1451C>G (chr10-89719435-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001284259.2(KIF20B):c.1451C>G(p.Thr484Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,585,928 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

KIF20B
NM_001284259.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.63

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.037310123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF20B	NM_001284259.2 link	c.1451C>G	p.Thr484Ser	missense_variant	Exon 13 of 33	ENST00000371728.8	NP_001271188.1	Q96Q89-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF20B	ENST00000371728.8 link	c.1451C>G	p.Thr484Ser	missense_variant	Exon 13 of 33	1	NM_001284259.2	ENSP00000360793.3		Q96Q89-1
KIF20B	ENST00000260753.8 link	c.1451C>G	p.Thr484Ser	missense_variant	Exon 13 of 33	1		ENSP00000260753.4		Q96Q89-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000173

AC:

AN:

231056

AF XY:

0.00000795

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000278

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000474

AC:

AN:

1433770

Hom.:

Cov.:

AF XY:

0.0000435

AC XY:

AN XY:

712482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31706

American (AMR)

AF:

0.0000262

AC:

AN:

38118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24802

East Asian (EAS)

AF:

0.00

AC:

AN:

39464

South Asian (SAS)

AF:

0.00

AC:

AN:

81572

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5230

European-Non Finnish (NFE)

AF:

0.0000590

AC:

AN:

1101166

Other (OTH)

AF:

0.0000339

AC:

AN:

59054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000850

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1451C>G (p.T484S) alteration is located in exon 13 (coding exon 12) of the KIF20B gene. This alteration results from a C to G substitution at nucleotide position 1451, causing the threonine (T) at amino acid position 484 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.21

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.015

.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M

PhyloP100

-1.6

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.80

N;N

REVEL

Benign

0.030

Sift

Benign

0.23

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.0040

B;B

Vest4

0.072

MutPred

0.27

Gain of disorder (P = 0.0318);Gain of disorder (P = 0.0318);

MVP

0.19

MPC

0.021

ClinPred

0.041

GERP RS

-2.8

Varity_R

0.054

gMVP

0.24

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over