NM_014809.4:c.3038A>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.3038A>G(p.Tyr1013Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,593,340 control chromosomes in the GnomAD database, including 14,484 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1131 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13353 hom. )

Consequence

KIAA0319
NM_014809.4 missense, splice_region

Scores

Splicing: ADA: 0.00006375

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.66

Publications

26 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=0.0016924143).

BP6

Variant 6-24551436-T-C is Benign according to our data. Variant chr6-24551436-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060890.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIAA0319	NM_014809.4	MANE Select	c.3038A>G	p.Tyr1013Cys	missense splice_region	Exon 20 of 21	NP_055624.2
KIAA0319	NM_001168375.2		c.3038A>G	p.Tyr1013Cys	missense splice_region	Exon 20 of 21	NP_001161847.1
KIAA0319	NM_001350403.2		c.3038A>G	p.Tyr1013Cys	missense splice_region	Exon 20 of 21	NP_001337332.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.3038A>G	p.Tyr1013Cys	missense splice_region	Exon 20 of 21	ENSP00000367459.3
KIAA0319	ENST00000616673.4	TSL:1	c.1271A>G	p.Tyr424Cys	missense splice_region	Exon 16 of 17	ENSP00000483665.1
KIAA0319	ENST00000537886.5	TSL:1	c.2858-4093A>G		intron	N/A	ENSP00000439700.1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17875

AN:

152100

Hom.:

1130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.0901

Gnomad ASJ

AF:

0.0787

Gnomad EAS

AF:

0.0820

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.119

AC:

29879

AN:

251242

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.0936

Gnomad AMR exome

AF:

0.0956

Gnomad ASJ exome

AF:

0.0740

Gnomad EAS exome

AF:

0.0905

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.132

AC:

190114

AN:

1441122

Hom.:

13353

Cov.:

AF XY:

0.131

AC XY:

94016

AN XY:

718186

show subpopulations

African (AFR)

AF:

0.0901

AC:

2986

AN:

33148

American (AMR)

AF:

0.0955

AC:

4269

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0734

AC:

1913

AN:

26058

East Asian (EAS)

AF:

0.0593

AC:

2348

AN:

39610

South Asian (SAS)

AF:

0.112

AC:

9578

AN:

85886

European-Finnish (FIN)

AF:

0.126

AC:

6708

AN:

53408

Middle Eastern (MID)

AF:

0.0876

AC:

503

AN:

5740

European-Non Finnish (NFE)

AF:

0.141

AC:

154038

AN:

1092892

Other (OTH)

AF:

0.130

AC:

7771

AN:

59686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

7097

14194

21292

28389

35486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5394

10788

16182

21576

26970

<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:

0.118

AC:

17897

AN:

152218

Hom.:

1131

Cov.:

AF XY:

0.114

AC XY:

8521

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0951

AC:

3950

AN:

41530

American (AMR)

AF:

0.0904

AC:

1382

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0787

AC:

273

AN:

3470

East Asian (EAS)

AF:

0.0822

AC:

426

AN:

5182

South Asian (SAS)

AF:

0.114

AC:

548

AN:

4824

European-Finnish (FIN)

AF:

0.123

AC:

1302

AN:

10588

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9622

AN:

68020

Other (OTH)

AF:

0.114

AC:

241

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

809

1618

2428

3237

4046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.129

Hom.:

5942

Bravo

AF:

0.114

TwinsUK

AF:

0.147

AC:

546

ALSPAC

AF:

0.148

AC:

571

ESP6500AA

AF:

0.0942

AC:

415

ESP6500EA

AF:

0.134

AC:

1149

ExAC

AF:

0.120

AC:

14582

Asia WGS

AF:

0.0960

AC:

334

AN:

3478

EpiCase

AF:

0.129

EpiControl

AF:

0.128

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

Eigen

Benign

0.17

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

1.7

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.097

Sift

Benign

0.20

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.28

MPC

0.55

ClinPred

0.026

GERP RS

0.20

Varity_R

0.11

gMVP

0.24

Mutation Taster

=89/11

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000064

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over