dbSNP rs1886997: KIF20B:p.Asn1219Thr (chr10-89738497-A-C) – 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.3656A>C(p.Asn1219Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,916 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

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: 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=0.06403631).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF20B	NM_001284259.2	MANE Select	c.3656A>C	p.Asn1219Thr	missense	Exon 20 of 33	NP_001271188.1	Q96Q89-1
KIF20B	NM_016195.4		c.3536A>C	p.Asn1179Thr	missense	Exon 20 of 33	NP_057279.2
KIF20B	NM_001382506.1		c.3443A>C	p.Asn1148Thr	missense	Exon 19 of 32	NP_001369435.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF20B	ENST00000371728.8	TSL:1 MANE Select	c.3656A>C	p.Asn1219Thr	missense	Exon 20 of 33	ENSP00000360793.3	Q96Q89-1
KIF20B	ENST00000260753.8	TSL:1	c.3536A>C	p.Asn1179Thr	missense	Exon 20 of 33	ENSP00000260753.4	Q96Q89-3
KIF20B	ENST00000478929.1	TSL:1	n.2202A>C		non_coding_transcript_exon	Exon 7 of 20

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74180

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41402

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67884

Other (OTH)

AF:

0.00

AC:

AN:

2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.049

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.47

M_CAP

Benign

0.027

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PhyloP100

0.14

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.65

REVEL

Benign

0.071

Sift

Uncertain

0.0030

Sift4G

Benign

0.27

Polyphen

0.034

Vest4

0.12

MutPred

0.075

Gain of phosphorylation at N1219 (P = 0.0406)

MVP

0.21

MPC

0.023

ClinPred

0.072

GERP RS

-0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.079

Mutation Taster

=91/9

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over