1-200617637-C-T

Position:

chr1-200617637-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014875.3(KIF14):c.1087G>A(p.Val363Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,611,654 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 17 hom. )

Consequence

KIF14
NM_014875.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.31

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016474038).

BP6

Variant 1-200617637-C-T is Benign according to our data. Variant chr1-200617637-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 435619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00251 (383/152360) while in subpopulation SAS AF= 0.00372 (18/4834). AF 95% confidence interval is 0.00319. There are 1 homozygotes in gnomad4. There are 192 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF14	NM_014875.3 linkuse as main transcript	c.1087G>A	p.Val363Ile	missense_variant	2/30	ENST00000367350.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF14	ENST00000367350.5 linkuse as main transcript	c.1087G>A	p.Val363Ile	missense_variant	2/30	2	NM_014875.3	P1
KIF14	ENST00000614960.4 linkuse as main transcript	c.1087G>A	p.Val363Ile	missense_variant	1/29	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

383

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00356

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00295

AC:

738

AN:

250560

Hom.:

AF XY:

0.00318

AC XY:

431

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00348

Gnomad FIN exome

AF:

0.00644

Gnomad NFE exome

AF:

0.00361

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00375

AC:

5468

AN:

1459294

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

2709

AN XY:

725634

show subpopulations

Gnomad4 AFR exome

AF:

0.000841

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.000460

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00384

Gnomad4 FIN exome

AF:

0.00594

Gnomad4 NFE exome

AF:

0.00408

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00251

AC:

383

AN:

152360

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00372

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.00356

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00337

Hom.:

Bravo

AF:

0.00231

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00269

AC:

327

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	KIF14: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 11, 2020

- -

Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome;C4693572:Microcephaly 20, primary, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 02, 2021

- -

KIF14-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

T;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.016

T;T

MetaSVM

Uncertain

-0.025

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.64

.;N

REVEL

Benign

0.24

Sift

Benign

0.19

.;T

Sift4G

Benign

0.15

T;T

Polyphen

0.99

D;D

Vest4

0.34

MVP

0.60

MPC

0.12

ClinPred

0.027

GERP RS

4.7

Varity_R

0.17

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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