rs2038135

Positions:

• chr6-24645739-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350404.2(KIAA0319):​c.34A>C​(p.Thr12Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,554 control chromosomes in the GnomAD database, including 37,902 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37812 hom., cov: 29)
  • Exomes 𝑓: 0.64 (90 hom.)
• Consequence: KIAA0319 NM_001350404.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.-109A>C		5_prime_UTR_variant	1/21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.-109A>C		5_prime_UTR_variant	1/21	1	NM_014809.4	ENSP00000367459.3
KIAA0319	ENST00000537886.5	c.-109A>C		5_prime_UTR_variant	1/19	1		ENSP00000439700.1
KIAA0319	ENST00000535378.5	c.-227A>C		5_prime_UTR_variant	1/22	2		ENSP00000442403.1
KIAA0319	ENST00000430948.6	c.-193A>C		5_prime_UTR_variant	1/20	2		ENSP00000401086.2

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106048 AN: 151022 Hom.: 37783 Cov.: 29

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.641 AC: 264 AN: 412 Hom.: 90 Cov.: 0 AF XY: 0.645 AC XY: 160 AN XY: 248

Gnomad4 AFR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.786

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.684

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.850

GnomAD4 genome AF: 0.702 AC: 106129 AN: 151142 Hom.: 37812 Cov.: 29 AF XY: 0.699 AC XY: 51571 AN XY: 73812

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.710

Alfa AF: 0.668 Hom.: 30139

Bravo AF: 0.724

Asia WGS AF: 0.790 AC: 2745 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.81

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: rs2038135; hg19: chr6-24645967;