Variant 12-39294187-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001173464.2(KIF21A):c.*237A>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 0.25 in 411,246 control chromosomes in the GnomAD database, including 16,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8435 hom., cov: 32)

Exomes 𝑓: 0.22 ( 7901 hom. )

Consequence

KIF21A
NM_001173464.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.49

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-39294187-T-C is Benign according to our data. Variant chr12-39294187-T-C is described in ClinVar as [Benign]. Clinvar id is 308542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21A	NM_001173464.2 linkuse as main transcript	c.*237A>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.*237A>G		3_prime_UTR_variant	38/38	1	NM_001173464.2	ENSP00000354878.5		Q7Z4S6-1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

45017

AN:

151924

Hom.:

8396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.528

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.223

AC:

57680

AN:

259204

Hom.:

7901

Cov.:

AF XY:

0.232

AC XY:

31692

AN XY:

136876

show subpopulations

Gnomad4 AFR exome

AF:

0.518

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.345

Gnomad4 SAS exome

AF:

0.383

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.179

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.297

AC:

45109

AN:

152042

Hom.:

8435

Cov.:

AF XY:

0.298

AC XY:

22137

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.529

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.379

Gnomad4 SAS

AF:

0.408

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.208

Hom.:

3751

Bravo

AF:

0.308

Asia WGS

AF:

0.393

AC:

1361

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.82

CADD

Benign

1.3

DANN

Benign

0.73

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