10-89711012-A-G

Position:

• chr10-89711012-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001284259.2(KIF20B):​c.542A>G​(p.Asp181Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 33)
• Consequence: KIF20B NM_001284259.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

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 (HGNC:):

ACMG classification

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=0.20996302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF20B	NM_001284259.2	c.542A>G	p.Asp181Gly	missense_variant	6/33	ENST00000371728.8	NP_001271188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF20B	ENST00000371728.8	c.542A>G	p.Asp181Gly	missense_variant	6/33	1	NM_001284259.2	ENSP00000360793.3
KIF20B	ENST00000260753.8	c.542A>G	p.Asp181Gly	missense_variant	6/33	1		ENSP00000260753.4
KIF20B	ENST00000447580.1	c.542A>G	p.Asp181Gly	missense_variant	6/6	5		ENSP00000390946.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 23, 2024

The c.542A>G (p.D181G) alteration is located in exon 6 (coding exon 5) of the KIF20B gene. This alteration results from a A to G substitution at nucleotide position 542, causing the aspartic acid (D) at amino acid position 181 to be replaced by a glycine (G). 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	-0.0070	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Uncertain	0.97
DEOGEN2	Benign	0.15	.;T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.79	N;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.028	B;B;.
Vest4		0.15
MutPred		0.56		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.45
MPC		0.055
ClinPred		0.11	T
GERP RS		3.0
Varity_R		0.069
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-91470769;