10-89738370-T-C

Variant names:

• chr10-89738370-T-C
• rs1886996
• NM_001284259.2:c.3529T>C

Variant summary

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

The NM_001284259.2(KIF20B):​c.3529T>C​(p.Cys1177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,608,090 control chromosomes in the GnomAD database, including 457,655 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.78 (46791 hom., cov: 32)
  • Exomes 𝑓: 0.75 (410864 hom.)
• Consequence: KIF20B NM_001284259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• Publications: 32 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=9.773138E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.911 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20B	NM_001284259.2	MANE Select	c.3529T>C	p.Cys1177Arg	missense	Exon 20 of 33	NP_001271188.1
	KIF20B	NM_016195.4		c.3409T>C	p.Cys1137Arg	missense	Exon 20 of 33	NP_057279.2
	KIF20B	NM_001382506.1		c.3316T>C	p.Cys1106Arg	missense	Exon 19 of 32	NP_001369435.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF20B	ENST00000371728.8	TSL:1 MANE Select	c.3529T>C	p.Cys1177Arg	missense	Exon 20 of 33	ENSP00000360793.3
	KIF20B	ENST00000260753.8	TSL:1	c.3409T>C	p.Cys1137Arg	missense	Exon 20 of 33	ENSP00000260753.4
	KIF20B	ENST00000478929.1	TSL:1	n.2075T>C		non_coding_transcript_exon	Exon 7 of 20

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118652 AN: 151814 Hom.: 46739 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.747

GnomAD2 exomes AF: 0.792 AC: 194973 AN: 246112 AF XY: 0.791

Gnomad AFR exome AF: 0.840

Gnomad AMR exome AF: 0.856

Gnomad ASJ exome AF: 0.715

Gnomad EAS exome AF: 0.923

Gnomad FIN exome AF: 0.790

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.757

GnomAD4 exome AF: 0.748 AC: 1089239 AN: 1456158 Hom.: 410864 Cov.: 39 AF XY: 0.752 AC XY: 544611 AN XY: 724156

African (AFR) AF: 0.836 AC: 27637 AN: 33068

American (AMR) AF: 0.846 AC: 36975 AN: 43692

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 18450 AN: 25900

East Asian (EAS) AF: 0.937 AC: 37103 AN: 39578

South Asian (SAS) AF: 0.926 AC: 78248 AN: 84488

European-Finnish (FIN) AF: 0.788 AC: 42033 AN: 53334

Middle Eastern (MID) AF: 0.694 AC: 3981 AN: 5738

European-Non Finnish (NFE) AF: 0.720 AC: 799803 AN: 1110218

Other (OTH) AF: 0.748 AC: 45009 AN: 60142

GnomAD4 genome AF: 0.782 AC: 118757 AN: 151932 Hom.: 46791 Cov.: 32 AF XY: 0.789 AC XY: 58582 AN XY: 74256

African (AFR) AF: 0.841 AC: 34910 AN: 41498

American (AMR) AF: 0.794 AC: 12131 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2560 AN: 3466

East Asian (EAS) AF: 0.925 AC: 4783 AN: 5170

South Asian (SAS) AF: 0.934 AC: 4506 AN: 4826

European-Finnish (FIN) AF: 0.806 AC: 8509 AN: 10560

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49028 AN: 67828

Other (OTH) AF: 0.751 AC: 1580 AN: 2104

Alfa AF: 0.730 Hom.: 79238

Bravo AF: 0.776

TwinsUK AF: 0.724 AC: 2685

ALSPAC AF: 0.740 AC: 2851

ESP6500AA AF: 0.843 AC: 3709

ESP6500EA AF: 0.713 AC: 6131

ExAC AF: 0.793 AC: 96233

Asia WGS AF: 0.925 AC: 3211 AN: 3474

EpiCase AF: 0.714

EpiControl AF: 0.708

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.5
DANN	Benign	0.31
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	9.8e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.54
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.074
Sift	Benign	0.18	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.035
MPC		0.023
ClinPred		0.018	T
GERP RS		0.46
Varity_R		0.12
gMVP		0.23
Mutation Taster		=100/0	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: rs1886996; hg19: chr10-91498127; COSMIC: COSV53308149;