rs75449932

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.3808A>C(p.Ser1270Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,610,398 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 56 hom. )

Consequence

KIF14
NM_014875.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.30

Publications

8 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=0.003931284).

BP6

Variant 1-200565523-T-G is Benign according to our data. Variant chr1-200565523-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0049 (746/152324) while in subpopulation NFE AF = 0.00756 (514/68020). AF 95% confidence interval is 0.00702. There are 1 homozygotes in GnomAd4. There are 366 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF14	NM_014875.3 link	c.3808A>C	p.Ser1270Arg	missense_variant	Exon 24 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.3808A>C	p.Ser1270Arg	missense_variant	Exon 24 of 30	2	NM_014875.3	ENSP00000356319.4		Q15058
KIF14	ENST00000614960.4 link	c.3808A>C	p.Ser1270Arg	missense_variant	Exon 23 of 29	1		ENSP00000483069.1		Q15058

Frequencies

GnomAD3 genomes

AF:

0.00490

AC:

746

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00756

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00564

AC:

1397

AN:

247832

AF XY:

0.00582

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.000803

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0121

Gnomad NFE exome

AF:

0.00906

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00660

AC:

9626

AN:

1458074

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

4594

AN XY:

725184

show subpopulations

African (AFR)

AF:

0.000992

AC:

AN:

33254

American (AMR)

AF:

0.00120

AC:

AN:

44046

Ashkenazi Jewish (ASJ)

AF:

0.000844

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39598

South Asian (SAS)

AF:

0.000635

AC:

AN:

85050

European-Finnish (FIN)

AF:

0.0123

AC:

657

AN:

53390

Middle Eastern (MID)

AF:

0.000738

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.00769

AC:

8542

AN:

1111032

Other (OTH)

AF:

0.00433

AC:

261

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

487

974

1461

1948

2435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.00490

AC:

746

AN:

152324

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

366

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41576

American (AMR)

AF:

0.00261

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0112

AC:

119

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00756

AC:

514

AN:

68020

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

121

161

201

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:

0.00703

Hom.:

Bravo

AF:

0.00424

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00559

AC:

ExAC

AF:

0.00632

AC:

767

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIF14: BP4, BS2 -

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 20, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.67

T;.

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.4

L;L

PhyloP100

2.3

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.0

.;N

REVEL

Benign

0.11

Sift

Benign

0.033

.;D

Sift4G

Benign

0.074

T;T

Polyphen

0.11

B;B

Vest4

0.26

MutPred

0.29

Loss of ubiquitination at K1273 (P = 0.0391);Loss of ubiquitination at K1273 (P = 0.0391);

MVP

0.59

MPC

0.12

ClinPred

0.0083

GERP RS

4.4

Varity_R

0.18

gMVP

0.24

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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