ENST00000537886.5:c.*3061C>T

Variant names:

• chr6-24544104-G-A
• rs2744605
• ENST00000537886.5:c.*3061C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000537886.5(KIAA0319):​c.*3061C>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 152,228 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.081 (715 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: KIAA0319 ENST00000537886.5 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000537886.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.*3061C>T		downstream_gene	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.*3061C>T		downstream_gene	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.*3061C>T		downstream_gene	N/A	NP_001337332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000537886.5	TSL:1	c.*3061C>T		splice_region	Exon 19 of 19	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.*3061C>T		splice_region	Exon 17 of 17	ENSP00000483665.1
	KIAA0319	ENST00000537886.5	TSL:1	c.*3061C>T		3_prime_UTR	Exon 19 of 19	ENSP00000439700.1

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12301 AN: 152110 Hom.: 712 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.00941

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0750

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0809 AC: 12314 AN: 152228 Hom.: 715 Cov.: 33 AF XY: 0.0825 AC XY: 6139 AN XY: 74414

African (AFR) AF: 0.157 AC: 6522 AN: 41514

American (AMR) AF: 0.0552 AC: 845 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3472

East Asian (EAS) AF: 0.00943 AC: 49 AN: 5194

South Asian (SAS) AF: 0.0419 AC: 202 AN: 4826

European-Finnish (FIN) AF: 0.136 AC: 1439 AN: 10590

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3009 AN: 68012

Other (OTH) AF: 0.0738 AC: 156 AN: 2114

Alfa AF: 0.0552 Hom.: 838

Bravo AF: 0.0787

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2744605; hg19: chr6-24544332;