Variant 10-89709936-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001284259.2(KIF20B):c.361C>T(p.Pro121Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000555 in 1,568,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

KIF20B
NM_001284259.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25106156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF20B	NM_001284259.2 link	c.361C>T	p.Pro121Ser	missense_variant	5/33	ENST00000371728.8	NP_001271188.1	Q96Q89-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIF20B	ENST00000371728.8 link	c.361C>T	p.Pro121Ser	missense_variant	5/33	1	NM_001284259.2	ENSP00000360793.3	Q96Q89-1
KIF20B	ENST00000260753.8 link	c.361C>T	p.Pro121Ser	missense_variant	5/33	1		ENSP00000260753.4	Q96Q89-3
KIF20B	ENST00000447580.1 link	c.361C>T	p.Pro121Ser	missense_variant	5/6	5		ENSP00000390946.1	A0A0A0MSJ5

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000101

AC:

AN:

218152

Hom.:

AF XY:

0.000101

AC XY:

AN XY:

118650

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000748

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000536

AC:

AN:

1416946

Hom.:

Cov.:

AF XY:

0.0000682

AC XY:

AN XY:

703616

show subpopulations

Gnomad4 AFR exome

AF:

0.000130

Gnomad4 AMR exome

AF:

0.0000292

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000732

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151986

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000289

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2023

The c.361C>T (p.P121S) alteration is located in exon 5 (coding exon 4) of the KIF20B gene. This alteration results from a C to T substitution at nucleotide position 361, causing the proline (P) at amino acid position 121 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

.;T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Uncertain

0.0041

MutationAssessor

Benign

1.7

L;L;.

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.4

D;D;D

REVEL

Uncertain

0.36

Sift

Benign

0.056

T;D;D

Sift4G

Uncertain

0.0090

D;D;T

Polyphen

0.076

B;D;.

Vest4

0.42

MVP

0.73

MPC

0.16

ClinPred

0.39

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over