Variant 11-28036445-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031217.4(KIF18A):c.2168T>C(p.Met723Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,610,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

KIF18A
NM_031217.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

Variant links:

Genes affected

KIF18A (HGNC:29441): (kinesin family member 18A) KIF18A is a member of the kinesin superfamily of microtubule-associated molecular motors (see MIM 148760) that use hydrolysis of ATP to produce force and movement along microtubules (Luboshits and Benayahu, 2005 [PubMed 15878648]).[supplied by OMIM, Aug 2008]

KIF18A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013540357).

BS2

High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF18A	NM_031217.4 linkuse as main transcript	c.2168T>C	p.Met723Thr	missense_variant	14/17	ENST00000263181.7	NP_112494.3	Q8NI77
KIF18A	XM_017018379.2 linkuse as main transcript	c.2168T>C	p.Met723Thr	missense_variant	14/17		XP_016873868.1	Q8NI77
KIF18A	XM_017018380.2 linkuse as main transcript	c.836T>C	p.Met279Thr	missense_variant	6/9		XP_016873869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF18A	ENST00000263181.7 linkuse as main transcript	c.2168T>C	p.Met723Thr	missense_variant	14/17	1	NM_031217.4	ENSP00000263181.6		Q8NI77

Frequencies

GnomAD3 genomes

AF:

0.000218

AC:

AN:

151526

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000325

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000392

AC:

AN:

249926

Hom.:

AF XY:

0.000377

AC XY:

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00190

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000594

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000286

AC:

417

AN:

1459282

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

726006

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00211

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000288

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000218

AC:

AN:

151526

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

AN XY:

73986

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000325

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000456

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000328

EpiControl

AF:

0.00119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.2168T>C (p.M723T) alteration is located in exon 14 (coding exon 13) of the KIF18A gene. This alteration results from a T to C substitution at nucleotide position 2168, causing the methionine (M) at amino acid position 723 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.35

M_CAP

Benign

0.026

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.26

REVEL

Benign

0.073

Sift

Benign

0.048

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.024

MVP

0.55

MPC

0.13

ClinPred

0.0096

GERP RS

-0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.086

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over