11-28036400-T-A

Position:

• chr11-28036400-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031217.4(KIF18A):​c.2213A>T​(p.Asn738Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: KIF18A NM_031217.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.173

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1996066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF18A	NM_031217.4	c.2213A>T	p.Asn738Ile	missense_variant	14/17	ENST00000263181.7	NP_112494.3
KIF18A	XM_017018379.2	c.2213A>T	p.Asn738Ile	missense_variant	14/17		XP_016873868.1
KIF18A	XM_017018380.2	c.881A>T	p.Asn294Ile	missense_variant	6/9		XP_016873869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF18A	ENST00000263181.7	c.2213A>T	p.Asn738Ile	missense_variant	14/17	1	NM_031217.4	ENSP00000263181.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.2213A>T (p.N738I) alteration is located in exon 14 (coding exon 13) of the KIF18A gene. This alteration results from a A to T substitution at nucleotide position 2213, causing the asparagine (N) at amino acid position 738 to be replaced by an isoleucine (I). 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	0.10
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	7.1
DANN	Benign	0.95
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.20
Sift	Benign	0.093	T
Sift4G	Benign	0.18	T
Polyphen		0.97	D
Vest4		0.23
MutPred		0.24		Loss of disorder (P = 0.0352);
MVP		0.83
MPC		0.17
ClinPred		0.43	T
GERP RS		5.7
Varity_R		0.097
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-28057947;