6-24551501-T-C

Variant names:

• chr6-24551501-T-C
• rs807535
• NM_014809.4:c.2973A>G

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.2973A>G​(p.Lys991Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,603,368 control chromosomes in the GnomAD database, including 15,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1133 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13909 hom.)
• Consequence: KIAA0319 NM_014809.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0180
• Publications: 12 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=-0.84).
• BP6: Variant 6-24551501-T-C is Benign according to our data. Variant chr6-24551501-T-C is described in ClinVar as [Benign]. Clinvar id is 3059378.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.018 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2973A>G	p.Lys991Lys	synonymous_variant	Exon 20 of 21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2973A>G	p.Lys991Lys	synonymous_variant	Exon 20 of 21	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17925 AN: 152040 Hom.: 1132 Cov.: 32

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.0821

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.119 AC: 29890 AN: 251138 AF XY: 0.120

Gnomad AFR exome AF: 0.0939

Gnomad AMR exome AF: 0.0961

Gnomad ASJ exome AF: 0.0740

Gnomad EAS exome AF: 0.0904

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.133 AC: 193517 AN: 1451210 Hom.: 13909 Cov.: 30 AF XY: 0.132 AC XY: 95534 AN XY: 722520

African (AFR) AF: 0.0913 AC: 3042 AN: 33318

American (AMR) AF: 0.0960 AC: 4291 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 1931 AN: 26088

East Asian (EAS) AF: 0.0595 AC: 2362 AN: 39666

South Asian (SAS) AF: 0.112 AC: 9613 AN: 86044

European-Finnish (FIN) AF: 0.126 AC: 6703 AN: 53402

Middle Eastern (MID) AF: 0.0885 AC: 509 AN: 5752

European-Non Finnish (NFE) AF: 0.143 AC: 157149 AN: 1102168

Other (OTH) AF: 0.132 AC: 7917 AN: 60072

GnomAD4 genome AF: 0.118 AC: 17947 AN: 152158 Hom.: 1133 Cov.: 32 AF XY: 0.115 AC XY: 8533 AN XY: 74400

African (AFR) AF: 0.0955 AC: 3965 AN: 41512

American (AMR) AF: 0.0921 AC: 1407 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3468

East Asian (EAS) AF: 0.0823 AC: 427 AN: 5190

South Asian (SAS) AF: 0.114 AC: 548 AN: 4826

European-Finnish (FIN) AF: 0.122 AC: 1293 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9636 AN: 67968

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.126 Hom.: 1981

Bravo AF: 0.115

Asia WGS AF: 0.0960 AC: 336 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.128

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

KIAA0319-related disorder Benign:1

Dec 23, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		-0.018
Mutation Taster		=99/1	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: rs807535; hg19: chr6-24551729; COSMIC: COSV65500550;