Genetic Variant KIF12:p.Arg575Gly (chr9-114092426-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001388308.1(KIF12):c.1723C>G(p.Arg575Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R575P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KIF12
NM_001388308.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.740

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

cholestasis
Inheritance: AR Classification: DEFINITIVE Submitted by: King Faisal Specialist Hospital and Research Center
cholestasis, progressive familial intrahepatic, 8
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

KIF12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06149736).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388308.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF12	NM_001388308.1	MANE Select	c.1723C>G	p.Arg575Gly	missense	Exon 18 of 19	NP_001375237.1	A0A1W2PPS5
	KIF12	NM_138424.2		c.1309C>G	p.Arg437Gly	missense	Exon 15 of 16	NP_612433.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF12	ENST00000640217.2	TSL:5 MANE Select	c.1723C>G	p.Arg575Gly	missense	Exon 18 of 19	ENSP00000491702.1	A0A1W2PPS5
KIF12	ENST00000640553.1	TSL:1	n.1547C>G		non_coding_transcript_exon	Exon 15 of 16
KIF12	ENST00000905877.1		c.1618C>G	p.Arg540Gly	missense	Exon 17 of 18	ENSP00000575936.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111732

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.026

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.61

M_CAP

Benign

0.039

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

PhyloP100

0.74

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.3

REVEL

Benign

0.15

Sift

Uncertain

0.0020

Sift4G

Benign

0.16

Polyphen

0.0010

Vest4

0.39

MutPred

0.12

Loss of MoRF binding (P = 0.0198)

MVP

0.38

MPC

0.24

ClinPred

0.22

GERP RS

-1.5

PromoterAI

0.0060

Neutral

(source)

Varity_R

0.094

gMVP

0.12

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over