6-24596250-T-G

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.424A>C(p.Thr142Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,614,112 control chromosomes in the GnomAD database, including 664,946 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).

Frequency

Genomes: 𝑓 0.91 ( 63527 hom., cov: 33)

Exomes 𝑓: 0.91 ( 601419 hom. )

Consequence

KIAA0319
NM_014809.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.800

Publications

40 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=5.99598E-7).

BP6

Variant 6-24596250-T-G is Benign according to our data. Variant chr6-24596250-T-G is described in ClinVar as Benign. ClinVar VariationId is 3059261.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.424A>C	p.Thr142Pro	missense_variant	Exon 3 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.424A>C	p.Thr142Pro	missense_variant	Exon 3 of 21	1	NM_014809.4	ENSP00000367459.3	Q5VV43-1
KIAA0319	ENST00000537886.5 link	c.424A>C	p.Thr142Pro	missense_variant	Exon 3 of 19	1		ENSP00000439700.1	Q5VV43-4
KIAA0319	ENST00000535378.5 link	c.397A>C	p.Thr133Pro	missense_variant	Exon 4 of 22	2		ENSP00000442403.1	Q5VV43-2
KIAA0319	ENST00000430948.6 link	c.289A>C	p.Thr97Pro	missense_variant	Exon 2 of 20	2		ENSP00000401086.2	Q5VV43-3

Frequencies

GnomAD3 genomes

AF:

0.913

AC:

138902

AN:

152144

Hom.:

63466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.925

Gnomad AMI

AF:

0.766

Gnomad AMR

AF:

0.935

Gnomad ASJ

AF:

0.917

Gnomad EAS

AF:

0.986

Gnomad SAS

AF:

0.936

Gnomad FIN

AF:

0.918

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.894

Gnomad OTH

AF:

0.908

GnomAD2 exomes

AF:

0.918

AC:

230511

AN:

251126

AF XY:

0.916

show subpopulations

Gnomad AFR exome

AF:

0.927

Gnomad AMR exome

AF:

0.952

Gnomad ASJ exome

AF:

0.911

Gnomad EAS exome

AF:

0.992

Gnomad FIN exome

AF:

0.909

Gnomad NFE exome

AF:

0.892

Gnomad OTH exome

AF:

0.916

GnomAD4 exome

AF:

0.907

AC:

1325577

AN:

1461850

Hom.:

601419

Cov.:

AF XY:

0.907

AC XY:

659254

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.924

AC:

30932

AN:

33478

American (AMR)

AF:

0.950

AC:

42466

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

23788

AN:

26134

East Asian (EAS)

AF:

0.977

AC:

38794

AN:

39700

South Asian (SAS)

AF:

0.936

AC:

80762

AN:

86254

European-Finnish (FIN)

AF:

0.906

AC:

48371

AN:

53404

Middle Eastern (MID)

AF:

0.867

AC:

5003

AN:

5768

European-Non Finnish (NFE)

AF:

0.900

AC:

1000273

AN:

1111992

Other (OTH)

AF:

0.914

AC:

55188

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

7602

15205

22807

30410

38012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21482

42964

64446

85928

107410

<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:

0.913

AC:

139022

AN:

152262

Hom.:

63527

Cov.:

AF XY:

0.916

AC XY:

68193

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.926

AC:

38464

AN:

41552

American (AMR)

AF:

0.935

AC:

14300

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.917

AC:

3183

AN:

3470

East Asian (EAS)

AF:

0.986

AC:

5099

AN:

5172

South Asian (SAS)

AF:

0.936

AC:

4515

AN:

4824

European-Finnish (FIN)

AF:

0.918

AC:

9751

AN:

10618

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.894

AC:

60836

AN:

68016

Other (OTH)

AF:

0.909

AC:

1919

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

629

1258

1886

2515

3144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.899

Hom.:

288498

Bravo

AF:

0.915

TwinsUK

AF:

0.909

AC:

3369

ALSPAC

AF:

0.902

AC:

3477

ESP6500AA

AF:

0.921

AC:

4057

ESP6500EA

AF:

0.896

AC:

7704

ExAC

AF:

0.914

AC:

111013

Asia WGS

AF:

0.960

AC:

3340

AN:

3478

EpiCase

AF:

0.897

EpiControl

AF:

0.888

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIAA0319-related disorder

Benign:1

Oct 17, 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

0.035

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.00059

.;.;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.064

T;T;T;.;T

MetaRNN

Benign

6.0e-7

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.0

.;N;.;N;N

PhyloP100

0.80

PrimateAI

Benign

0.43

PROVEAN

Benign

1.6

N;N;N;N;N

REVEL

Benign

0.039

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.81

T;T;T;T;T

Polyphen

0.0

.;.;B;B;B

Vest4

0.072

MPC

0.14

ClinPred

0.0012

GERP RS

2.5

Varity_R

0.12

gMVP

0.25

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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