rs807541

Variant names:

• chr6-24559053-A-G
• rs807541
• NM_014809.4:c.2694T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_014809.4(KIAA0319):​c.2694T>C​(p.Ala898Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,612,098 control chromosomes in the GnomAD database, including 40,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (2956 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37469 hom.)
• Consequence: KIAA0319 NM_014809.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.72
• Publications: 15 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-24559053-A-G is Benign according to our data. Variant chr6-24559053-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060711.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 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.2694T>C	p.Ala898Ala	synonymous	Exon 17 of 21	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.2694T>C	p.Ala898Ala	synonymous	Exon 17 of 21	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.2694T>C	p.Ala898Ala	synonymous	Exon 17 of 21	NP_001337332.1	Q5VV43-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.2694T>C	p.Ala898Ala	synonymous	Exon 17 of 21	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.2694T>C	p.Ala898Ala	synonymous	Exon 17 of 19	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.927T>C	p.Ala309Ala	synonymous	Exon 13 of 17	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29112 AN: 152080 Hom.: 2948 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.201 AC: 50042 AN: 248788 AF XY: 0.204

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.135

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.223 AC: 325627 AN: 1459900 Hom.: 37469 Cov.: 33 AF XY: 0.223 AC XY: 161734 AN XY: 726128

African (AFR) AF: 0.136 AC: 4534 AN: 33452

American (AMR) AF: 0.181 AC: 8029 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2853 AN: 26094

East Asian (EAS) AF: 0.112 AC: 4427 AN: 39672

South Asian (SAS) AF: 0.233 AC: 20055 AN: 85950

European-Finnish (FIN) AF: 0.213 AC: 11367 AN: 53340

Middle Eastern (MID) AF: 0.125 AC: 699 AN: 5584

European-Non Finnish (NFE) AF: 0.235 AC: 260633 AN: 1111006

Other (OTH) AF: 0.216 AC: 13030 AN: 60338

GnomAD4 genome AF: 0.191 AC: 29144 AN: 152198 Hom.: 2956 Cov.: 33 AF XY: 0.188 AC XY: 14012 AN XY: 74400

African (AFR) AF: 0.143 AC: 5945 AN: 41522

American (AMR) AF: 0.172 AC: 2636 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3468

East Asian (EAS) AF: 0.125 AC: 649 AN: 5184

South Asian (SAS) AF: 0.236 AC: 1139 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 2173 AN: 10594

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15417 AN: 68002

Other (OTH) AF: 0.189 AC: 400 AN: 2112

Alfa AF: 0.207 Hom.: 6805

Bravo AF: 0.187

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KIAA0319-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.2
DANN	Benign	0.48
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: rs807541; hg19: chr6-24559281; COSMIC: COSV65498588;