chr1-200553438-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014875.3(KIF14):c.4897C>G(p.Pro1633Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,613,436 control chromosomes in the GnomAD database, including 117,543 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.29 ( 7722 hom., cov: 31)

Exomes 𝑓: 0.38 ( 109821 hom. )

Consequence

KIF14
NM_014875.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0450

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.403029E-4).

BP6

Variant 1-200553438-G-C is Benign according to our data. Variant chr1-200553438-G-C is described in ClinVar as [Benign]. Clinvar id is 1223272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF14	NM_014875.3 link	c.4897C>G	p.Pro1633Ala	missense_variant	Exon 30 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.4897C>G	p.Pro1633Ala	missense_variant	Exon 30 of 30	2	NM_014875.3	ENSP00000356319.4		Q15058
KIF14	ENST00000614960.4 link	c.4897C>G	p.Pro1633Ala	missense_variant	Exon 29 of 29	1		ENSP00000483069.1		Q15058

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43678

AN:

151794

Hom.:

7725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0913

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.401

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.344

GnomAD2 exomes

AF:

0.318

AC:

79911

AN:

251216

AF XY:

0.330

show subpopulations

Gnomad AFR exome

AF:

0.0859

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.379

AC:

554322

AN:

1461524

Hom.:

109821

Cov.:

AF XY:

0.380

AC XY:

275957

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0762

AC:

2550

AN:

33476

Gnomad4 AMR exome

AF:

0.199

AC:

8876

AN:

44712

Gnomad4 ASJ exome

AF:

0.435

AC:

11355

AN:

26122

Gnomad4 EAS exome

AF:

0.240

AC:

9514

AN:

39700

Gnomad4 SAS exome

AF:

0.312

AC:

26925

AN:

86216

Gnomad4 FIN exome

AF:

0.265

AC:

14166

AN:

53418

Gnomad4 NFE exome

AF:

0.411

AC:

456804

AN:

1111738

Gnomad4 Remaining exome

AF:

0.363

AC:

21912

AN:

60378

Heterozygous variant carriers

17428

34856

52284

69712

87140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

13830

27660

41490

55320

69150

<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:

0.288

AC:

43675

AN:

151912

Hom.:

7722

Cov.:

AF XY:

0.280

AC XY:

20795

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.0912

AC:

0.0911919

AN:

0.0911919

Gnomad4 AMR

AF:

0.267

AC:

0.266689

AN:

0.266689

Gnomad4 ASJ

AF:

0.446

AC:

0.44611

AN:

0.44611

Gnomad4 EAS

AF:

0.232

AC:

0.231669

AN:

0.231669

Gnomad4 SAS

AF:

0.309

AC:

0.308506

AN:

0.308506

Gnomad4 FIN

AF:

0.263

AC:

0.262688

AN:

0.262688

Gnomad4 NFE

AF:

0.406

AC:

0.406404

AN:

0.406404

Gnomad4 OTH

AF:

0.344

AC:

0.343661

AN:

0.343661

Heterozygous variant carriers

1451

2903

4354

5806

7257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.385

Hom.:

8895

Bravo

AF:

0.280

TwinsUK

AF:

0.413

AC:

1532

ALSPAC

AF:

0.417

AC:

1606

ESP6500AA

AF:

0.103

AC:

454

ESP6500EA

AF:

0.410

AC:

3523

ExAC

AF:

0.320

AC:

38810

Asia WGS

AF:

0.230

AC:

802

AN:

3478

EpiCase

AF:

0.416

EpiControl

AF:

0.418

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Microcephaly 20, primary, autosomal recessive

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.0

DANN

Benign

0.82

DEOGEN2

Benign

0.057

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.41

T;.

MetaRNN

Benign

0.00064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.1

.;N

REVEL

Benign

0.048

Sift

Benign

0.091

.;T

Sift4G

Benign

0.16

T;T

Polyphen

0.31

B;B

Vest4

0.039

MPC

0.080

ClinPred

0.0043

GERP RS

0.60

Varity_R

0.036

gMVP

0.12

Mutation Taster

=100/0

polymorphism (auto)

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