10-89738370-T-C

Position:

• chr10-89738370-T-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

KIF20B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF20B	NM_001284259.2	c.3529T>C	p.Cys1177Arg	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.3529T>C	p.Cys1177Arg	missense_variant	20/33	1	NM_001284259.2	ENSP00000360793.3
KIF20B	ENST00000260753.8	c.3409T>C	p.Cys1137Arg	missense_variant	20/33	1		ENSP00000260753.4
KIF20B	ENST00000478929.1	n.2075T>C		non_coding_transcript_exon_variant	7/20	1

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

GnomAD3 exomes AF: 0.792 AC: 194973 AN: 246112 Hom.: 78193 AF XY: 0.791 AC XY: 105204 AN XY: 133064

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 SAS exome AF: 0.930

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

Gnomad4 AFR exome AF: 0.836

Gnomad4 AMR exome AF: 0.846

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.937

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.788

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 0.748

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

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.751

Alfa AF: 0.727 Hom.: 62749

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 v4.3

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;T
MetaRNN	Benign	9.8e-7	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.074
Sift	Benign	0.18	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.0	B;B
Vest4		0.035
MPC		0.023
ClinPred		0.018	T
GERP RS		0.46
Varity_R		0.12
gMVP		0.23

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: rs1886996; hg19: chr10-91498127; COSMIC: COSV53308149;