Genetic Variant KIF20A:p.Ser44Phe (chr5-138179811-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005733.3(KIF20A):c.131C>T(p.Ser44Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0037 in 1,614,062 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 17 hom. )

Consequence

KIF20A
NM_005733.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.81

Publications

10 publications found

Variant links:

Genes affected

KIF20A (HGNC:9787): (kinesin family member 20A) Enables protein kinase binding activity. Involved in microtubule bundle formation; midbody abscission; and regulation of cytokinesis. Located in several cellular components, including cleavage furrow; intercellular bridge; and midbody. Implicated in restrictive cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

KIF20A Gene-Disease associations (from GenCC):

familial isolated restrictive cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital heart disease
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
cardiomyopathy, familial restrictive, 6
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

KIF20A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0081786215).

BP6

Variant 5-138179811-C-T is Benign according to our data. Variant chr5-138179811-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 776591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 434 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005733.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20A	NM_005733.3	MANE Select	c.131C>T	p.Ser44Phe	missense	Exon 2 of 19	NP_005724.1	O95235-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF20A	ENST00000394894.8	TSL:1 MANE Select	c.131C>T	p.Ser44Phe	missense	Exon 2 of 19	ENSP00000378356.3	O95235-1
KIF20A	ENST00000927201.1		c.131C>T	p.Ser44Phe	missense	Exon 2 of 19	ENSP00000597260.1
KIF20A	ENST00000927194.1		c.131C>T	p.Ser44Phe	missense	Exon 2 of 19	ENSP00000597253.1

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

434

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00288

AC:

724

AN:

251336

AF XY:

0.00278

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00566

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00419

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00379

AC:

5535

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

2723

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33480

American (AMR)

AF:

0.00344

AC:

154

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00677

AC:

177

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.00108

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00434

AC:

4825

AN:

1112004

Other (OTH)

AF:

0.00384

AC:

232

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

291

582

873

1164

1455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

186

372

558

744

930

<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:

0.00285

AC:

434

AN:

152194

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

200

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41530

American (AMR)

AF:

0.00360

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00187

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00451

AC:

307

AN:

68018

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

110

138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00369

Hom.:

Bravo

AF:

0.00314

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00288

AC:

350

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00523

EpiControl

AF:

0.00658

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0082

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.0

PhyloP100

5.8

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.27

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.43

MVP

0.85

MPC

2.4

ClinPred

0.028

GERP RS

4.6

Varity_R

0.47

gMVP

0.67

Mutation Taster

=88/12

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over