chr10-89727892-A-T

Variant names:

• chr10-89727892-A-T
• rs12572012
• NM_001284259.2:c.2267A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001284259.2(KIF20B):​c.2267A>T​(p.Asn756Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,536,074 control chromosomes in the GnomAD database, including 34,622 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.18 (3136 hom., cov: 32)
  • Exomes 𝑓: 0.21 (31486 hom.)
• Consequence: KIF20B NM_001284259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 22 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00417462).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

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.2267A>T	p.Asn756Ile	missense	Exon 17 of 33	NP_001271188.1	Q96Q89-1
	KIF20B	NM_016195.4		c.2147A>T	p.Asn716Ile	missense	Exon 17 of 33	NP_057279.2
	KIF20B	NM_001382506.1		c.2054A>T	p.Asn685Ile	missense	Exon 16 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.2267A>T	p.Asn756Ile	missense	Exon 17 of 33	ENSP00000360793.3	Q96Q89-1
	KIF20B	ENST00000260753.8	TSL:1	c.2147A>T	p.Asn716Ile	missense	Exon 17 of 33	ENSP00000260753.4	Q96Q89-3
	KIF20B	ENST00000478929.1	TSL:1	n.813A>T		non_coding_transcript_exon	Exon 4 of 20

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28116 AN: 152016 Hom.: 3139 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.199

GnomAD2 exomes AF: 0.217 AC: 51243 AN: 236060 AF XY: 0.217

Gnomad AFR exome AF: 0.0702

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.326

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.220

GnomAD4 exome AF: 0.206 AC: 285294 AN: 1383938 Hom.: 31486 Cov.: 29 AF XY: 0.206 AC XY: 141980 AN XY: 689156

African (AFR) AF: 0.0642 AC: 2045 AN: 31852

American (AMR) AF: 0.209 AC: 8164 AN: 39070

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 4448 AN: 24794

East Asian (EAS) AF: 0.330 AC: 12526 AN: 37934

South Asian (SAS) AF: 0.218 AC: 17919 AN: 82102

European-Finnish (FIN) AF: 0.291 AC: 14774 AN: 50780

Middle Eastern (MID) AF: 0.148 AC: 821 AN: 5566

European-Non Finnish (NFE) AF: 0.202 AC: 213269 AN: 1054708

Other (OTH) AF: 0.198 AC: 11328 AN: 57132

GnomAD4 genome AF: 0.185 AC: 28109 AN: 152136 Hom.: 3136 Cov.: 32 AF XY: 0.191 AC XY: 14195 AN XY: 74376

African (AFR) AF: 0.0729 AC: 3027 AN: 41534

American (AMR) AF: 0.188 AC: 2873 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1802 AN: 5178

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4822

European-Finnish (FIN) AF: 0.317 AC: 3334 AN: 10524

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14702 AN: 67992

Other (OTH) AF: 0.197 AC: 415 AN: 2110

Alfa AF: 0.209 Hom.: 2593

Bravo AF: 0.170

TwinsUK AF: 0.227 AC: 840

ALSPAC AF: 0.203 AC: 781

ESP6500AA AF: 0.0723 AC: 316

ESP6500EA AF: 0.203 AC: 1737

ExAC AF: 0.218 AC: 26433

Asia WGS AF: 0.271 AC: 940 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.34
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.023
Sift	Benign	0.044	D
Sift4G	Benign	0.19	T
Polyphen		0.0030	B
Vest4		0.12
MPC		0.021
ClinPred		0.015	T
GERP RS		1.1
Varity_R		0.096
gMVP		0.10
Mutation Taster		=95/5	polymorphism (auto)

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: rs12572012; hg19: chr10-91487649; COSMIC: COSV53305837;