1-200617637-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/22 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:6

Conservation

PhyloP100: 2.31

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive primary microcephaly
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
microcephaly 20, primary, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

KIF14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF14	NM_014875.3 link	c.1087G>A	p.Val363Ile	missense_variant	Exon 2 of 30	ENST00000367350.5	NP_055690.1	Q15058

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF14	ENST00000367350.5 link	c.1087G>A	p.Val363Ile	missense_variant	Exon 2 of 30	2	NM_014875.3	ENSP00000356319.4		Q15058
KIF14	ENST00000614960.4 link	c.1087G>A	p.Val363Ile	missense_variant	Exon 1 of 29	1		ENSP00000483069.1		Q15058

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

GnomAD2 exomes

AF:

0.00295

AC:

738

AN:

250560

AF XY:

0.00318

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 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

African (AFR)

AF:

0.000841

AC:

AN:

33304

American (AMR)

AF:

0.00182

AC:

AN:

44442

Ashkenazi Jewish (ASJ)

AF:

0.000460

AC:

AN:

26076

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39642

South Asian (SAS)

AF:

0.00384

AC:

331

AN:

86120

European-Finnish (FIN)

AF:

0.00594

AC:

317

AN:

53396

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00408

AC:

4526

AN:

1110292

Other (OTH)

AF:

0.00270

AC:

163

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

268

536

803

1071

1339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00251

AC:

383

AN:

152360

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000673

AC:

AN:

41586

American (AMR)

AF:

0.00235

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00372

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00490

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00356

AC:

242

AN:

68038

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00331

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIF14: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Sep 11, 2020

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

KIF14-related disorder

Benign:1

Oct 01, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

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

Benign:1

Sep 02, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

2.3

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

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over