dbSNP rs2744559: KIAA0319:p.Gly567Ser (chr6-24576403-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014809.4(KIAA0319):c.1699G>A(p.Gly567Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0318 in 1,613,952 control chromosomes in the GnomAD database, including 2,527 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.077 ( 1105 hom., cov: 32)

Exomes 𝑓: 0.027 ( 1422 hom. )

Consequence

KIAA0319
NM_014809.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.15

Publications

12 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015474856).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.1699G>A	p.Gly567Ser	missense_variant	Exon 10 of 21	ENST00000378214.8	NP_055624.2	Q5VV43-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8 link	c.1699G>A	p.Gly567Ser	missense_variant	Exon 10 of 21	1	NM_014809.4	ENSP00000367459.3		Q5VV43-1

Frequencies

GnomAD3 genomes

AF:

0.0772

AC:

11742

AN:

152006

Hom.:

1099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00302

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0617

GnomAD2 exomes

AF:

0.0287

AC:

7221

AN:

251360

AF XY:

0.0237

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.000870

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0271

AC:

39611

AN:

1461828

Hom.:

1422

Cov.:

AF XY:

0.0255

AC XY:

18573

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.239

AC:

7990

AN:

33472

American (AMR)

AF:

0.0205

AC:

917

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00696

AC:

182

AN:

26136

East Asian (EAS)

AF:

0.000605

AC:

AN:

39700

South Asian (SAS)

AF:

0.00240

AC:

207

AN:

86258

European-Finnish (FIN)

AF:

0.00314

AC:

168

AN:

53420

Middle Eastern (MID)

AF:

0.0246

AC:

142

AN:

5766

European-Non Finnish (NFE)

AF:

0.0251

AC:

27953

AN:

1111960

Other (OTH)

AF:

0.0336

AC:

2028

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1888

3776

5665

7553

9441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1230

2460

3690

4920

6150

<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:

0.0774

AC:

11779

AN:

152124

Hom.:

1105

Cov.:

AF XY:

0.0741

AC XY:

5514

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.231

AC:

9553

AN:

41444

American (AMR)

AF:

0.0346

AC:

529

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.00208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00302

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0218

AC:

1481

AN:

68016

Other (OTH)

AF:

0.0611

AC:

129

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

495

991

1486

1982

2477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0407

Hom.:

1030

Bravo

AF:

0.0877

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0270

AC:

104

ESP6500AA

AF:

0.225

AC:

991

ESP6500EA

AF:

0.0210

AC:

181

ExAC

AF:

0.0326

AC:

3960

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0198

EpiControl

AF:

0.0204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0030

.;.;.;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.78

T;T;T;.;T

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.47

.;N;.;N;N

PhyloP100

4.1

PrimateAI

Benign

0.41

PROVEAN

Benign

0.62

N;N;N;N;N

REVEL

Benign

0.076

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.027, 0.034

.;.;B;B;B

Vest4

0.055

MPC

0.12

ClinPred

0.015

GERP RS

3.0

Varity_R

0.091

gMVP

0.30

Mutation Taster

=98/2

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

Computational scores

Splicing

Publications

Other links and lift over