chr10-89738497-A-T

Variant names:

• chr10-89738497-A-T
• rs1886997
• NM_001284259.2:c.3656A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001284259.2(KIF20B):​c.3656A>T​(p.Asn1219Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KIF20B NM_001284259.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08291942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF20B	NM_001284259.2	c.3656A>T	p.Asn1219Ile	missense_variant	Exon 20 of 33	ENST00000371728.8	NP_001271188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF20B	ENST00000371728.8	c.3656A>T	p.Asn1219Ile	missense_variant	Exon 20 of 33	1	NM_001284259.2	ENSP00000360793.3
KIF20B	ENST00000260753.8	c.3536A>T	p.Asn1179Ile	missense_variant	Exon 20 of 33	1		ENSP00000260753.4
KIF20B	ENST00000478929.1	n.2202A>T		non_coding_transcript_exon_variant	Exon 7 of 20	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454288 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723144

African (AFR) AF: 0.00 AC: 0 AN: 33048

American (AMR) AF: 0.00 AC: 0 AN: 43750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39518

South Asian (SAS) AF: 0.00 AC: 0 AN: 83990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108840

Other (OTH) AF: 0.00 AC: 0 AN: 60104

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.058	.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	.;N
PhyloP100		0.14
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.058	T;T
Polyphen		0.14	B;B
Vest4		0.18
MutPred		0.12		.;Gain of methylation at K1221 (P = 0.0421);
MVP		0.23
MPC		0.050
ClinPred		0.11	T
GERP RS		-0.72
Varity_R		0.22
gMVP		0.18
Mutation Taster		=92/8	polymorphism

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: rs1886997; hg19: chr10-91498254;