rs75449932

Positions:

chr1-200565523-T-G

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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=0.003931284).

BP6

Variant 1-200565523-T-G is Benign according to our data. Variant chr1-200565523-T-G is described in ClinVar as [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF14	NM_014875.3 linkuse as main transcript	c.3808A>C	p.Ser1270Arg	missense_variant	24/30	ENST00000367350.5	NP_055690.1	Q15058

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF14	ENST00000367350.5 linkuse as main transcript	c.3808A>C	p.Ser1270Arg	missense_variant	24/30	2	NM_014875.3	ENSP00000356319.4		Q15058
KIF14	ENST00000614960.4 linkuse as main transcript	c.3808A>C	p.Ser1270Arg	missense_variant	23/29	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

GnomAD3 exomes

AF:

0.00564

AC:

1397

AN:

247832

Hom.:

AF XY:

0.00582

AC XY:

779

AN XY:

133856

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 SAS exome

AF:

0.000921

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

Gnomad4 AFR exome

AF:

0.000992

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.000844

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000635

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.00769

Gnomad4 OTH exome

AF:

0.00433

GnomAD4 genome

AF:

0.00490

AC:

746

AN:

152324

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

366

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.00756

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00650

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

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	KIF14: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 20, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

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

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

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

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

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