Variant 12-39293779-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001173464.2(KIF21A):c.*645T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000817 in 153,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

KIF21A
NM_001173464.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.37

Variant links:

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]

KIF21A links:

KIF21A (HGNC:):

KIF21A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 12-39293779-A-C is Benign according to our data. Variant chr12-39293779-A-C is described in ClinVar as [Benign]. Clinvar id is 308536.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21A	NM_001173464.2 linkuse as main transcript	c.*645T>G		3_prime_UTR_variant	38/38	ENST00000361418.10	NP_001166935.1	Q7Z4S6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF21A	ENST00000361418 linkuse as main transcript	c.*645T>G		3_prime_UTR_variant	38/38	1	NM_001173464.2	ENSP00000354878.5		Q7Z4S6-1

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.000957

GnomAD4 exome

AF:

0.00122

AC:

AN:

820

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

AN XY:

522

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00318

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000814

AC:

124

AN:

152242

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000476

Hom.:

Bravo

AF:

0.000782

Asia WGS

AF:

0.00261

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital fibrosis of extraocular muscles type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.8

DANN

Benign

0.84

Splicing

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