Genetic Variant KIF12:p.Ala641Thr (chr9-114091896-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001388308.1(KIF12):c.1921G>A(p.Ala641Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00077 in 1,611,398 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 11 hom. )

Consequence

KIF12
NM_001388308.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.10

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036716163).

BP6

Variant 9-114091896-C-T is Benign according to our data. Variant chr9-114091896-C-T is described in ClinVar as [Benign]. Clinvar id is 2051148.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000906 (138/152312) while in subpopulation EAS AF= 0.0135 (70/5172). AF 95% confidence interval is 0.011. There are 1 homozygotes in gnomad4. There are 76 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF12	NM_001388308.1 link	c.1921G>A	p.Ala641Thr	missense_variant	Exon 19 of 19	ENST00000640217.2	NP_001375237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF12	ENST00000640217.2 link	c.1921G>A	p.Ala641Thr	missense_variant	Exon 19 of 19	5	NM_001388308.1	ENSP00000491702.1		A0A1W2PPS5

Frequencies

GnomAD3 genomes

AF:

0.000913

AC:

139

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.0137

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00159

AC:

394

AN:

247918

Hom.:

AF XY:

0.00155

AC XY:

209

AN XY:

134514

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000500

Gnomad EAS exome

AF:

0.0136

Gnomad SAS exome

AF:

0.00236

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.000316

Gnomad OTH exome

AF:

0.000823

GnomAD4 exome

AF:

0.000756

AC:

1103

AN:

1459086

Hom.:

Cov.:

AF XY:

0.000830

AC XY:

602

AN XY:

725494

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.000537

Gnomad4 EAS exome

AF:

0.0125

Gnomad4 SAS exome

AF:

0.00255

Gnomad4 FIN exome

AF:

0.00125

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152312

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.0135

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000361

Hom.:

Bravo

AF:

0.000812

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00161

AC:

195

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.068

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.0010

DANN

Benign

0.17

DEOGEN2

Benign

0.0033

.;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.41

T;T;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.27

PROVEAN

Benign

0.21

.;N;.

REVEL

Benign

0.089

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

.;T;.

Polyphen

0.0

.;.;B

Vest4

0.036

MVP

0.081

MPC

0.16

ClinPred

0.0071

GERP RS

-7.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.024

gMVP

0.089

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