NM_014809.4:c.*42A>G

Variant names:

• chr6-24547123-T-C
• rs7770041
• NM_014809.4:c.*42A>G

Variant summary

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

The NM_014809.4(KIAA0319):​c.*42A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 1,603,148 control chromosomes in the GnomAD database, including 868 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 0.041 (267 hom., cov: 33)
  • Exomes 𝑓: 0.022 (601 hom.)
• Consequence: KIAA0319 NM_014809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.*42A>G		3_prime_UTR	Exon 21 of 21	NP_055624.2
	KIAA0319	NM_001168375.2		c.*42A>G		3_prime_UTR	Exon 21 of 21	NP_001161847.1
	KIAA0319	NM_001350403.2		c.*42A>G		3_prime_UTR	Exon 21 of 21	NP_001337332.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.*42A>G		3_prime_UTR	Exon 21 of 21	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.*42A>G		3_prime_UTR	Exon 19 of 19	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.*42A>G		3_prime_UTR	Exon 17 of 17	ENSP00000483665.1

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6224 AN: 152200 Hom.: 264 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0320

GnomAD2 exomes AF: 0.0186 AC: 4647 AN: 249378 AF XY: 0.0163

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.00172

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.00337

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.0131

GnomAD4 exome AF: 0.0224 AC: 32453 AN: 1450830 Hom.: 601 Cov.: 28 AF XY: 0.0213 AC XY: 15417 AN XY: 722122

African (AFR) AF: 0.113 AC: 3759 AN: 33218

American (AMR) AF: 0.0117 AC: 521 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00174 AC: 45 AN: 25894

East Asian (EAS) AF: 0.000505 AC: 20 AN: 39628

South Asian (SAS) AF: 0.00203 AC: 174 AN: 85584

European-Finnish (FIN) AF: 0.00345 AC: 183 AN: 53098

Middle Eastern (MID) AF: 0.0185 AC: 106 AN: 5738

European-Non Finnish (NFE) AF: 0.0238 AC: 26220 AN: 1103038

Other (OTH) AF: 0.0237 AC: 1425 AN: 60026

GnomAD4 genome AF: 0.0409 AC: 6234 AN: 152318 Hom.: 267 Cov.: 33 AF XY: 0.0381 AC XY: 2835 AN XY: 74476

African (AFR) AF: 0.107 AC: 4428 AN: 41556

American (AMR) AF: 0.0182 AC: 278 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0205 AC: 1396 AN: 68036

Other (OTH) AF: 0.0317 AC: 67 AN: 2116

Alfa AF: 0.0269 Hom.: 150

Bravo AF: 0.0454

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.86
PhyloP100		-0.62
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: rs7770041; hg19: chr6-24547351;