chr10-89709936-C-T

Variant names:

• chr10-89709936-C-T
• rs372714100
• NM_001284259.2:c.361C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001284259.2(KIF20B):​c.361C>T​(p.Pro121Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000555 in 1,568,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: KIF20B NM_001284259.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67
• Publications: 0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25106156).

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.361C>T	p.Pro121Ser	missense	Exon 5 of 33	NP_001271188.1	Q96Q89-1
	KIF20B	NM_016195.4		c.361C>T	p.Pro121Ser	missense	Exon 5 of 33	NP_057279.2
	KIF20B	NM_001382506.1		c.361C>T	p.Pro121Ser	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.361C>T	p.Pro121Ser	missense	Exon 5 of 33	ENSP00000360793.3	Q96Q89-1
	KIF20B	ENST00000260753.8	TSL:1	c.361C>T	p.Pro121Ser	missense	Exon 5 of 33	ENSP00000260753.4	Q96Q89-3
	KIF20B	ENST00000919433.1		c.274C>T	p.Pro92Ser	missense	Exon 4 of 32	ENSP00000589492.1

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 12 AN: 151868 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000101 AC: 22 AN: 218152 AF XY: 0.000101

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000536 AC: 76 AN: 1416946 Hom.: 0 Cov.: 30 AF XY: 0.0000682 AC XY: 48 AN XY: 703616

African (AFR) AF: 0.000130 AC: 4 AN: 30882

American (AMR) AF: 0.0000292 AC: 1 AN: 34236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23956

East Asian (EAS) AF: 0.00 AC: 0 AN: 38950

South Asian (SAS) AF: 0.000732 AC: 57 AN: 77910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.0000119 AC: 13 AN: 1094902

Other (OTH) AF: 0.0000172 AC: 1 AN: 58252

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 151986 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74268

African (AFR) AF: 0.000145 AC: 6 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67964

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.0000289 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000115 AC: 14

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	Uncertain	0.35
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.0041	D
MutationAssessor	Benign	1.7	L
PhyloP100		3.7
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.36
Sift	Benign	0.056	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.076	B
Vest4		0.42
MVP		0.73
MPC		0.16
ClinPred		0.39	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.60
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs372714100; hg19: chr10-91469693;