Variant 9-114092347-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388308.1(KIF12):c.1802C>T(p.Ser601Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000629 in 1,591,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

KIF12
NM_001388308.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

Variant links:

Genes affected

KIF12 (HGNC:21495): (kinesin family member 12) This gene encodes a member of the kinesin superfamily of microtubule-associated molecular motors with functions related to the microtubule cytosekelton. Members of this superfamily play important roles in intracellular transport and cell division. A similar protein in mouse functions in the beta cell antioxidant signaling cascade, acting as a scaffold for the transcription factor specificity protein 1 (Sp1). Mice that lack this gene exhibit beta cell oxidative stress resulting in hypoinsulinemic glucose intolerance. [provided by RefSeq, Jul 2016]

KIF12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.108843654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF12	NM_001388308.1 linkuse as main transcript	c.1802C>T	p.Ser601Leu	missense_variant	18/19	ENST00000640217.2	NP_001375237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF12	ENST00000640217.2 linkuse as main transcript	c.1802C>T	p.Ser601Leu	missense_variant	18/19	5	NM_001388308.1	ENSP00000491702	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000857

AC:

AN:

233458

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

126420

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000573

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000556

AC:

AN:

1438940

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

714430

show subpopulations

Gnomad4 AFR exome

AF:

0.0000934

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000674

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2022

The c.1388C>T (p.S463L) alteration is located in exon 15 (coding exon 13) of the KIF12 gene. This alteration results from a C to T substitution at nucleotide position 1388, causing the serine (S) at amino acid position 463 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0099

.;.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.2

.;.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.64

.;N;.

REVEL

Benign

0.17

Sift

Uncertain

0.024

.;D;.

Sift4G

Uncertain

0.035

.;D;.

Polyphen

0.18

.;.;B

Vest4

0.23

MutPred

0.13

.;.;Loss of phosphorylation at S596 (P = 0.0248);

MVP

0.66

MPC

0.24

ClinPred

0.13

GERP RS

4.7

Varity_R

0.093

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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