rs374850339

Variant names:

• chr9-114091931-C-G
• rs374850339
• NM_001388308.1:c.1886G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-114091931-C-G
• chr9-114091931-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001388308.1(KIF12):​c.1886G>C​(p.Arg629Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIF12 NM_001388308.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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 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=0.12861171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF12	NM_001388308.1	c.1886G>C	p.Arg629Pro	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	c.1886G>C	p.Arg629Pro	missense_variant	Exon 19 of 19	5	NM_001388308.1	ENSP00000491702.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000408 AC: 1 AN: 245286 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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: 6.85e-7 AC: 1 AN: 1460216 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726410

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	.;.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.85	T
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.43	.;N;.
REVEL	Benign	0.20
Sift	Uncertain	0.0020	.;D;.
Sift4G	Uncertain	0.0060	.;D;.
Polyphen		0.96	.;.;P
Vest4		0.37
MutPred		0.19		.;.;Loss of MoRF binding (P = 0.0014);
MVP		0.40
MPC		0.62
ClinPred		0.82	D
GERP RS		0.89
Varity_R		0.19
gMVP		0.22

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

Other links and lift over

dbSNP: rs374850339; hg19: chr9-116854211;