6-24544739-C-T

Variant names:

• chr6-24544739-C-T
• rs16889440
• NM_014809.4:c.*2426G>A

Variant summary

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

The NM_014809.4(KIAA0319):​c.*2426G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,152 control chromosomes in the GnomAD database, including 2,221 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 0.16 (2221 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: KIAA0319 NM_014809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.*2426G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.*2426G>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24160 AN: 152026 Hom.: 2217 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

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) AF: 0.125 AC: 1 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.159 AC: 24175 AN: 152144 Hom.: 2221 Cov.: 32 AF XY: 0.158 AC XY: 11747 AN XY: 74392

African (AFR) AF: 0.249 AC: 10325 AN: 41478

American (AMR) AF: 0.121 AC: 1856 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3466

East Asian (EAS) AF: 0.0969 AC: 502 AN: 5180

South Asian (SAS) AF: 0.160 AC: 772 AN: 4824

European-Finnish (FIN) AF: 0.100 AC: 1060 AN: 10590

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8539 AN: 68010

Other (OTH) AF: 0.162 AC: 343 AN: 2114

Alfa AF: 0.139 Hom.: 7137

Bravo AF: 0.164

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.59
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs16889440; hg19: chr6-24544967;