rs1886996

chr10-89738370-T-Achr10-89738370-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001284259.2(KIF20B):c.3529T>A(p.Cys1177Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. C1177R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037365288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF20B	NM_001284259.2	c.3529T>A	p.Cys1177Ser	missense_variant	20/33	ENST00000371728.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF20B	ENST00000371728.8	c.3529T>A	p.Cys1177Ser	missense_variant	20/33	1	NM_001284259.2	A2
KIF20B	ENST00000260753.8	c.3409T>A	p.Cys1137Ser	missense_variant	20/33	1		P4
KIF20B	ENST00000478929.1	n.2075T>A		non_coding_transcript_exon_variant	7/20	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246112 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133064

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000297

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456558 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 724342

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000229

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	2.6
Dann	Benign	0.22
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.82	N;N
REVEL	Benign	0.063
Sift	Benign	0.42	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.0010	B;B
Vest4		0.21
MutPred		0.35		.;Gain of disorder (P = 0.0374);
MVP		0.28
MPC		0.027
ClinPred		0.044	T
GERP RS		0.46
Varity_R		0.058
gMVP		0.12

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;