Genetic Variant NM_001284259.2:c.365C>T (chr10-89709940-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001284259.2(KIF20B):c.365C>T(p.Ala122Val) variant causes a missense change. The variant allele was found at a frequency of 0.000014 in 1,429,392 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 1 hom. )

Consequence

KIF20B
NM_001284259.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF20B	NM_001284259.2 link	c.365C>T	p.Ala122Val	missense_variant	Exon 5 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.365C>T	p.Ala122Val	missense_variant	Exon 5 of 33	1	NM_001284259.2	ENSP00000360793.3	Q96Q89-1
KIF20B	ENST00000260753.8 link	c.365C>T	p.Ala122Val	missense_variant	Exon 5 of 33	1		ENSP00000260753.4	Q96Q89-3
KIF20B	ENST00000447580.1 link	c.365C>T	p.Ala122Val	missense_variant	Exon 5 of 6	5		ENSP00000390946.1	A0A0A0MSJ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000140

AC:

AN:

1429392

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

710362

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.365C>T (p.A122V) 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 365, causing the alanine (A) at amino acid position 122 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.059

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.73

N;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.0070

D;D;T

Polyphen

0.016

B;B;.

Vest4

0.31

MutPred

0.41

Loss of ubiquitination at K126 (P = 0.065);Loss of ubiquitination at K126 (P = 0.065);Loss of ubiquitination at K126 (P = 0.065);

MVP

0.49

MPC

0.024

ClinPred

0.59

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.053

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: 26

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over