12-39340188-C-T

Position:

• chr12-39340188-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP6_Moderate

The NM_001173464.2(KIF21A):​c.2287G>A​(p.Val763Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF21A NM_001173464.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.82

Genes affected

KIF21A (HGNC:19349): (kinesin family member 21A) This gene encodes a member of the KIF4 subfamily of kinesin-like motor proteins. The encoded protein is characterized by an N-terminal motor domain a coiled-coil stalk domain and a C-terminal WD-40 repeat domain. This protein may be involved in microtubule dependent transport. Mutations in this gene are the cause of congenital fibrosis of extraocular muscles-1. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KIF21A. . Gene score misZ 2.653 (greater than the threshold 3.09). Trascript score misZ 3.1091 (greater than threshold 3.09). GenCC has associacion of gene with congenital fibrosis of extraocular muscles, congenital fibrosis of extraocular muscles type 1.
• BP6: Variant 12-39340188-C-T is Benign according to our data. Variant chr12-39340188-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 221953.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21A	NM_001173464.2	c.2287G>A	p.Val763Met	missense_variant	16/38	ENST00000361418.10	NP_001166935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF21A	ENST00000361418.10	c.2287G>A	p.Val763Met	missense_variant	16/38	1	NM_001173464.2	ENSP00000354878.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital aniridia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Paul Sabatier University EA-4555, Paul Sabatier University

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;.;.;T;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.6	.;.;.;M;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.8	.;N;N;N;N
REVEL	Benign	0.29
Sift	Uncertain	0.0040	.;D;D;D;D
Sift4G	Uncertain	0.0050	.;D;D;D;D
Polyphen		1.0, 0.97	.;D;.;D;.
Vest4		0.53, 0.53, 0.68, 0.53
MutPred		0.32		.;.;.;Gain of methylation at K758 (P = 0.1111);.;
MVP		0.65
MPC		0.89
ClinPred		0.79	D
GERP RS		5.6
Varity_R		0.17
gMVP		0.27

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: rs869025264; hg19: chr12-39733990;