9-114092411-T-A

Variant names:

• chr9-114092411-T-A
• NM_001388308.1:c.1738A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001388308.1(KIF12):​c.1738A>T​(p.Met580Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF12 NM_001388308.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.00400

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05987391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF12	NM_001388308.1	c.1738A>T	p.Met580Leu	missense_variant	Exon 18 of 19	ENST00000640217.2	NP_001375237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF12	ENST00000640217.2	c.1738A>T	p.Met580Leu	missense_variant	Exon 18 of 19	5	NM_001388308.1	ENSP00000491702.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

KIF12-related disorder Uncertain:1

Aug 23, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The KIF12 c.1324A>T variant is predicted to result in the amino acid substitution p.Met442Leu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.71
DEOGEN2	Benign	0.012	.;.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;.;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.59	.;N;.
REVEL	Benign	0.083
Sift	Benign	0.14	.;T;.
Sift4G	Benign	0.60	.;T;.
Polyphen		0.0	.;.;B
Vest4		0.24
MutPred		0.22		.;.;Loss of catalytic residue at V571 (P = 0.0368);
MVP		0.50
MPC		0.15
ClinPred		0.067	T
GERP RS		-0.41
Varity_R		0.059
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-116854691;