12-39293733-G-GA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001173464.2(KIF21A):c.*690_*691insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 139,160 control chromosomes in the GnomAD database, including 1,373 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.091 (1373 hom., cov: 28)
  • Exomes 𝑓: 0.0052 (0 hom.)
• Consequence: KIF21A NM_001173464.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.298

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF21A	NM_001173464.2	c.*690_*691insT		3_prime_UTR_variant	38/38	ENST00000361418.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF21A	ENST00000361418.10	c.*690_*691insT		3_prime_UTR_variant	38/38	1	NM_001173464.2	A1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 12615 AN: 138740 Hom.: 1373 Cov.: 28

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.00346

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0365

Gnomad EAS AF: 0.0182

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0377

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.00521 AC: 2 AN: 384 Hom.: 0 Cov.: 0 AF XY: 0.00442 AC XY: 1 AN XY: 226

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0833

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0909 AC: 12620 AN: 138776 Hom.: 1373 Cov.: 28 AF XY: 0.0885 AC XY: 5937 AN XY: 67064

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.0450

Gnomad4 ASJ AF: 0.0365

Gnomad4 EAS AF: 0.0180

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.0749

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital fibrosis of extraocular muscles Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34373131; hg19: chr12-39687535;