10-89738497-A-G

Position:

• chr10-89738497-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001284259.2(KIF20B):​c.3656A>G​(p.Asn1219Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,604,082 control chromosomes in the GnomAD database, including 58,824 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.31 (8382 hom., cov: 33)
  • Exomes 𝑓: 0.25 (50442 hom.)
• Consequence: KIF20B NM_001284259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.440282E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF20B	NM_001284259.2	c.3656A>G	p.Asn1219Ser	missense_variant	20/33	ENST00000371728.8	NP_001271188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF20B	ENST00000371728.8	c.3656A>G	p.Asn1219Ser	missense_variant	20/33	1	NM_001284259.2	ENSP00000360793.3
KIF20B	ENST00000260753.8	c.3536A>G	p.Asn1179Ser	missense_variant	20/33	1		ENSP00000260753.4
KIF20B	ENST00000478929.1	n.2202A>G		non_coding_transcript_exon_variant	7/20	1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47364 AN: 151846 Hom.: 8355 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.263

GnomAD3 exomes AF: 0.281 AC: 68733 AN: 244886 Hom.: 10652 AF XY: 0.286 AC XY: 37964 AN XY: 132568

Gnomad AFR exome AF: 0.475

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.289

Gnomad EAS exome AF: 0.298

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.255 AC: 370192 AN: 1452116 Hom.: 50442 Cov.: 33 AF XY: 0.260 AC XY: 187667 AN XY: 722122

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.436

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.312 AC: 47422 AN: 151966 Hom.: 8382 Cov.: 33 AF XY: 0.314 AC XY: 23295 AN XY: 74270

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.271

Alfa AF: 0.249 Hom.: 12568

Bravo AF: 0.311

TwinsUK AF: 0.236 AC: 875

ALSPAC AF: 0.248 AC: 957

ESP6500AA AF: 0.455 AC: 1966

ESP6500EA AF: 0.230 AC: 1972

ExAC AF: 0.288 AC: 34860

Asia WGS AF: 0.411 AC: 1426 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.8
DANN	Benign	0.13
DEOGEN2	Benign	0.0062	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.00064	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.6	.;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.54	N;N
REVEL	Benign	0.095
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.027
MPC		0.018
ClinPred		0.0041	T
GERP RS		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.021
gMVP		0.054

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

Publications

LitVar

Other links and lift over

dbSNP: rs1886997; hg19: chr10-91498254; COSMIC: COSV53304374;