dbSNP rs2744550: KIAA0319:p.Ser773Gly (chr6-24564316-T-C) – 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.2317A>G(p.Ser773Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,613,302 control chromosomes in the GnomAD database, including 1,214 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 0.050 ( 421 hom., cov: 32)

Exomes 𝑓: 0.023 ( 793 hom. )

Consequence

KIAA0319
NM_014809.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.176

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001576066).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.2317A>G	p.Ser773Gly	missense_variant	Exon 15 of 21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8 link	c.2317A>G	p.Ser773Gly	missense_variant	Exon 15 of 21	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7569

AN:

152092

Hom.:

419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0417

GnomAD2 exomes

AF:

0.0209

AC:

5230

AN:

250664

AF XY:

0.0180

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.000870

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0151

GnomAD4 exome

AF:

0.0234

AC:

34210

AN:

1461092

Hom.:

793

Cov.:

AF XY:

0.0223

AC XY:

16209

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.146

AC:

4880

AN:

33396

American (AMR)

AF:

0.0132

AC:

591

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

26132

East Asian (EAS)

AF:

0.000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00189

AC:

163

AN:

86256

European-Finnish (FIN)

AF:

0.00343

AC:

183

AN:

53420

Middle Eastern (MID)

AF:

0.0199

AC:

115

AN:

5766

European-Non Finnish (NFE)

AF:

0.0240

AC:

26665

AN:

1111338

Other (OTH)

AF:

0.0256

AC:

1546

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

1561

3122

4683

6244

7805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1132

2264

3396

4528

5660

<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:

0.0498

AC:

7576

AN:

152210

Hom.:

421

Cov.:

AF XY:

0.0468

AC XY:

3481

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.137

AC:

5671

AN:

41496

American (AMR)

AF:

0.0224

AC:

343

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.00228

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00320

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0207

AC:

1409

AN:

68002

Other (OTH)

AF:

0.0412

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

345

690

1034

1379

1724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0303

Hom.:

432

Bravo

AF:

0.0561

TwinsUK

AF:

0.0243

AC:

ALSPAC

AF:

0.0257

AC:

ESP6500AA

AF:

0.133

AC:

586

ESP6500EA

AF:

0.0199

AC:

171

ExAC

AF:

0.0230

AC:

2794

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0189

EpiControl

AF:

0.0196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.99

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.0095

.;.;.;.;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.047

T;T;T;T;.;T

MetaRNN

Benign

0.0016

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

.;.;M;.;M;M

PhyloP100

0.18

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.8

.;N;N;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.42

.;T;T;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T;T

Polyphen

0.0010, 0.0020

.;.;.;B;B;B

Vest4

0.052

MPC

0.098

ClinPred

0.0084

GERP RS

-1.5

Varity_R

0.057

gMVP

0.34

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

Computational scores

Splicing

Publications

Other links and lift over