12-39293733-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001173464.2(KIF21A):c.*690del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 138,988 control chromosomes in the GnomAD database, including 944 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (944 hom., cov: 28)
  • Exomes 𝑓: 0.41 (0 hom.)
• Consequence: KIF21A NM_001173464.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B: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 -10 ACMG points.

• BP6: Variant 12-39293733-GA-G is Benign according to our data. Variant chr12-39293733-GA-G is described in ClinVar as [Benign]. Clinvar id is 308534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.117 AC: 16152 AN: 138614 Hom.: 940 Cov.: 28

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.405 AC: 137 AN: 338 Hom.: 0 Cov.: 0 AF XY: 0.418 AC XY: 82 AN XY: 196

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.117 AC: 16180 AN: 138650 Hom.: 944 Cov.: 28 AF XY: 0.121 AC XY: 8129 AN XY: 66984

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0600

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.0848

Gnomad4 OTH AF: 0.109

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital fibrosis of extraocular muscles Benign:1

Benign, 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;