6-24588656-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_014809.4(KIAA0319):c.931G>A(p.Ala311Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,612,676 control chromosomes in the GnomAD database, including 121,819 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A311G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.29 ( 8414 hom., cov: 31)

Exomes 𝑓: 0.38 ( 113405 hom. )

Consequence

KIAA0319
NM_014809.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.51

Publications

60 publications found

Variant links:

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]

KIAA0319 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.960599E-5).

BP6

Variant 6-24588656-C-T is Benign according to our data. Variant chr6-24588656-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056331.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.931G>A	p.Ala311Thr	missense_variant	Exon 4 of 21	ENST00000378214.8	NP_055624.2	Q5VV43-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIAA0319	ENST00000378214.8 link	c.931G>A	p.Ala311Thr	missense_variant	Exon 4 of 21	1	NM_014809.4	ENSP00000367459.3	Q5VV43-1
KIAA0319	ENST00000537886.5 link	c.931G>A	p.Ala311Thr	missense_variant	Exon 4 of 19	1		ENSP00000439700.1	Q5VV43-4
KIAA0319	ENST00000535378.5 link	c.904G>A	p.Ala302Thr	missense_variant	Exon 5 of 22	2		ENSP00000442403.1	Q5VV43-2
KIAA0319	ENST00000430948.6 link	c.796G>A	p.Ala266Thr	missense_variant	Exon 3 of 20	2		ENSP00000401086.2	Q5VV43-3

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44757

AN:

151694

Hom.:

8410

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0823

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.517

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.330

AC:

83069

AN:

251386

AF XY:

0.339

show subpopulations

Gnomad AFR exome

AF:

0.0730

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.514

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.383

AC:

560176

AN:

1460864

Hom.:

113405

Cov.:

AF XY:

0.382

AC XY:

277615

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.0674

AC:

2255

AN:

33474

American (AMR)

AF:

0.213

AC:

9528

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

9628

AN:

26130

East Asian (EAS)

AF:

0.124

AC:

4918

AN:

39696

South Asian (SAS)

AF:

0.304

AC:

26177

AN:

86238

European-Finnish (FIN)

AF:

0.510

AC:

27218

AN:

53416

Middle Eastern (MID)

AF:

0.188

AC:

1081

AN:

5764

European-Non Finnish (NFE)

AF:

0.412

AC:

458208

AN:

1111062

Other (OTH)

AF:

0.351

AC:

21163

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

16532

33064

49597

66129

82661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13796

27592

41388

55184

68980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.295

AC:

44776

AN:

151812

Hom.:

8414

Cov.:

AF XY:

0.300

AC XY:

22257

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.0827

AC:

3425

AN:

41438

American (AMR)

AF:

0.252

AC:

3837

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1302

AN:

3466

East Asian (EAS)

AF:

0.129

AC:

668

AN:

5160

South Asian (SAS)

AF:

0.299

AC:

1432

AN:

4786

European-Finnish (FIN)

AF:

0.517

AC:

5424

AN:

10492

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.409

AC:

27806

AN:

67904

Other (OTH)

AF:

0.275

AC:

580

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1433

2866

4300

5733

7166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.357

Hom.:

21236

Bravo

AF:

0.263

TwinsUK

AF:

0.410

AC:

1520

ALSPAC

AF:

0.403

AC:

1554

ESP6500AA

AF:

0.0960

AC:

423

ESP6500EA

AF:

0.404

AC:

3471

ExAC

AF:

0.328

AC:

39787

Asia WGS

AF:

0.216

AC:

753

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIAA0319-related disorder

Benign:1

Oct 21, 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

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.078

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.0011

.;.;.;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.22

T;T;T;.;T

MetaRNN

Benign

0.000080

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.58

.;N;.;N;N

PhyloP100

-1.5

PrimateAI

Benign

0.21

PROVEAN

Benign

0.71

N;N;N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.73

T;T;T;T;T

Sift4G

Benign

0.71

T;T;T;T;T

Polyphen

0.0020, 0.0010

.;.;B;B;B

Vest4

0.028

MPC

0.10

ClinPred

0.0055

GERP RS

-4.6

Varity_R

0.020

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over