Variant 1-200553393-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014875.3(KIF14):c.4942G>A(p.Val1648Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,830 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 (★). Synonymous variant affecting the same amino acid position (i.e. V1648V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KIF14
NM_014875.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

Variant links:

Genes affected

KIF14 (HGNC:19181): (kinesin family member 14) This gene encodes a member of the kinesin-3 superfamily of microtubule motor proteins. These proteins are involved in numerous processes including vesicle transport, chromosome segregation, mitotic spindle formation, and cytokinesis. In human HeLa-S3 and 293T cells, this protein is localized to the cytoplasm during interphase, to the spindle poles and spindle microtubules during mitosis, and to the midbody during cytokinesis. An internal motor domain displays microtubule-dependent ATPase activity, consistent with its function as a microtubule motor protein. Knockdown of this gene results in failed cytokinesis with endoreplication, which results in multinucleated cells. This gene has been identified as a likely oncogene in breast, lung and ovarian cancers, as well as retinoblastomas and gliomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

KIF14 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40099528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF14	NM_014875.3 link	c.4942G>A	p.Val1648Met	missense_variant	30/30	ENST00000367350.5	NP_055690.1	Q15058

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF14	ENST00000367350.5 link	c.4942G>A	p.Val1648Met	missense_variant	30/30	2	NM_014875.3	ENSP00000356319.4		Q15058
KIF14	ENST00000614960.4 link	c.4942G>A	p.Val1648Met	missense_variant	29/29	1		ENSP00000483069.1		Q15058

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000415

AC:

AN:

240828

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129984

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000909

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1448830

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719820

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.4942G>A (p.V1648M) alteration is located in exon 30 (coding exon 29) of the KIF14 gene. This alteration results from a G to A substitution at nucleotide position 4942, causing the valine (V) at amino acid position 1648 to be replaced by a methionine (M). 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

Uncertain

0.48

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.68

T;.

M_CAP

Benign

0.047

MetaRNN

Benign

0.40

T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.5

.;N

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.35

MutPred

0.27

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.79

MPC

0.46

ClinPred

0.90

GERP RS

5.3

Varity_R

0.29

gMVP

0.19

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