NM_001284259.2:c.361C>G

Variant names:

• chr10-89709936-C-G
• rs372714100
• NM_001284259.2:c.361C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001284259.2(KIF20B):​c.361C>G​(p.Pro121Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000191 in 1,568,818 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P121S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KIF20B NM_001284259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20B	NM_001284259.2	MANE Select	c.361C>G	p.Pro121Ala	missense	Exon 5 of 33	NP_001271188.1	Q96Q89-1
	KIF20B	NM_016195.4		c.361C>G	p.Pro121Ala	missense	Exon 5 of 33	NP_057279.2
	KIF20B	NM_001382506.1		c.361C>G	p.Pro121Ala	missense	Exon 5 of 32	NP_001369435.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20B	ENST00000371728.8	TSL:1 MANE Select	c.361C>G	p.Pro121Ala	missense	Exon 5 of 33	ENSP00000360793.3	Q96Q89-1
	KIF20B	ENST00000260753.8	TSL:1	c.361C>G	p.Pro121Ala	missense	Exon 5 of 33	ENSP00000260753.4	Q96Q89-3
	KIF20B	ENST00000919433.1		c.274C>G	p.Pro92Ala	missense	Exon 4 of 32	ENSP00000589492.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151870 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416948 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 703616

African (AFR) AF: 0.00 AC: 0 AN: 30882

American (AMR) AF: 0.00 AC: 0 AN: 34236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23956

East Asian (EAS) AF: 0.00 AC: 0 AN: 38950

South Asian (SAS) AF: 0.00 AC: 0 AN: 77910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1094904

Other (OTH) AF: 0.00 AC: 0 AN: 58252

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151870 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74142

African (AFR) AF: 0.0000484 AC: 2 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.046	D
MutationAssessor	Benign	1.9	M
PhyloP100		3.7
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.012	D
Polyphen		0.20	B
Vest4		0.47
MutPred		0.65		Gain of catalytic residue at P121 (P = 0.0212)
MVP		0.75
MPC		0.16
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.50
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs372714100; hg19: chr10-91469693;