NM_001284259.2:c.397A>G

Variant names:

• chr10-89709972-A-G
• rs149777607
• NM_001284259.2:c.397A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001284259.2(KIF20B):​c.397A>G​(p.Ile133Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,610,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: KIF20B NM_001284259.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008906543).

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.397A>G	p.Ile133Val	missense	Exon 5 of 33	NP_001271188.1	Q96Q89-1
	KIF20B	NM_016195.4		c.397A>G	p.Ile133Val	missense	Exon 5 of 33	NP_057279.2
	KIF20B	NM_001382506.1		c.397A>G	p.Ile133Val	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.397A>G	p.Ile133Val	missense	Exon 5 of 33	ENSP00000360793.3	Q96Q89-1
	KIF20B	ENST00000260753.8	TSL:1	c.397A>G	p.Ile133Val	missense	Exon 5 of 33	ENSP00000260753.4	Q96Q89-3
	KIF20B	ENST00000919433.1		c.310A>G	p.Ile104Val	missense	Exon 4 of 32	ENSP00000589492.1

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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

GnomAD2 exomes AF: 0.000149 AC: 37 AN: 248316 AF XY: 0.0000820

Gnomad AFR exome AF: 0.00205

Gnomad AMR exome AF: 0.0000593

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000480 AC: 70 AN: 1458194 Hom.: 0 Cov.: 30 AF XY: 0.0000386 AC XY: 28 AN XY: 725342

African (AFR) AF: 0.00183 AC: 61 AN: 33256

American (AMR) AF: 0.0000454 AC: 2 AN: 44094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39616

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110736

Other (OTH) AF: 0.0000664 AC: 4 AN: 60198

GnomAD4 genome AF: 0.000618 AC: 94 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.000565 AC XY: 42 AN XY: 74364

African (AFR) AF: 0.00224 AC: 93 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000120 Hom.: 0

Bravo AF: 0.000597

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000140 AC: 17

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0089	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.71	N
PhyloP100		1.9
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.083
Sift	Benign	0.62	T
Sift4G	Benign	0.85	T
Polyphen		0.020	B
Vest4		0.19
MVP		0.27
MPC		0.14
ClinPred		0.032	T
GERP RS		2.0
Varity_R		0.024
gMVP		0.21
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs149777607; hg19: chr10-91469729;