Variant 1-200553473-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014875.3(KIF14):c.4862T>C(p.Val1621Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

KIF14
NM_014875.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.639

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 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=0.06338072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF14	NM_014875.3 linkuse as main transcript	c.4862T>C	p.Val1621Ala	missense_variant	30/30	ENST00000367350.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF14	ENST00000367350.5 linkuse as main transcript	c.4862T>C	p.Val1621Ala	missense_variant	30/30	2	NM_014875.3	P1
KIF14	ENST00000614960.4 linkuse as main transcript	c.4862T>C	p.Val1621Ala	missense_variant	29/29	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000113

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 29, 2021

The c.4862T>C (p.V1621A) alteration is located in exon 30 (coding exon 29) of the KIF14 gene. This alteration results from a T to C substitution at nucleotide position 4862, causing the valine (V) at amino acid position 1621 to be replaced by an alanine (A). 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

0.47

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.3

DANN

Benign

0.93

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.43

T;.

M_CAP

Benign

0.070

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

Sift4G

Benign

0.19

T;T

Polyphen

0.0030

B;B

Vest4

0.071

MutPred

0.19

Loss of methylation at K1619 (P = 0.0876);Loss of methylation at K1619 (P = 0.0876);

MVP

0.76

MPC

0.10

ClinPred

0.11

GERP RS

0.51

Varity_R

0.044

gMVP

0.13

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