6-24579957-CA-CAA

Position:

• chr6-24579957-CA-CAA

Variant summary

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

The NM_014809.4(KIAA0319):​c.1280-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,565,220 control chromosomes in the GnomAD database, including 29,274 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3775 hom., cov: 26)
  • Exomes 𝑓: 0.18 (25499 hom.)
• Consequence: KIAA0319 NM_014809.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568

Genes affected

KIAA0319 (HGNC:21580): (KIAA0319) This gene encodes a transmembrane protein that contains a large extracellular domain with multiple polycystic kidney disease (PKD) domains. The encoded protein may play a role in the development of the cerebral cortex by regulating neuronal migration and cell adhesion. Single nucleotide polymorphisms in this gene are associated with dyslexia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.1280-8dupT		splice_region_variant, intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.1280-8dupT		splice_region_variant, intron_variant		1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31125 AN: 151486 Hom.: 3772 Cov.: 26

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0914

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.194

GnomAD3 exomes AF: 0.234 AC: 42833 AN: 182878 Hom.: 5745 AF XY: 0.223 AC XY: 21685 AN XY: 97422

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.413

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.501

Gnomad SAS exome AF: 0.177

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.180 AC: 253926 AN: 1413616 Hom.: 25499 Cov.: 28 AF XY: 0.178 AC XY: 124564 AN XY: 700344

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.525

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.206 AC: 31159 AN: 151604 Hom.: 3775 Cov.: 26 AF XY: 0.213 AC XY: 15739 AN XY: 74050

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.194

Bravo AF: 0.209

Asia WGS AF: 0.308 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3215493; hg19: chr6-24580185;