Variant 6-24551436-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4 linkuse as main transcript	c.3038A>G	p.Tyr1013Cys	missense_variant, splice_region_variant	20/21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8 linkuse as main transcript	c.3038A>G	p.Tyr1013Cys	missense_variant, splice_region_variant	20/21	1	NM_014809.4	ENSP00000367459	P2	Q5VV43-1

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

GnomAD3 exomes

AF:

0.119

AC:

29879

AN:

251242

Hom.:

1900

AF XY:

0.119

AC XY:

16220

AN XY:

135798

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 SAS exome

AF:

0.115

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

Gnomad4 AFR exome

AF:

0.0901

Gnomad4 AMR exome

AF:

0.0955

Gnomad4 ASJ exome

AF:

0.0734

Gnomad4 EAS exome

AF:

0.0593

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.118

AC:

17897

AN:

152218

Hom.:

1131

Cov.:

AF XY:

0.114

AC XY:

8521

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0951

Gnomad4 AMR

AF:

0.0904

Gnomad4 ASJ

AF:

0.0787

Gnomad4 EAS

AF:

0.0822

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.129

Hom.:

3305

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 23, 2019

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

0.17

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

.;.;.;T;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.90

D;T;T;.;T

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;.;.;M;M

MutationTaster

Benign

0.13

P;P;P;P;P

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.7

.;D;D;D;D

REVEL

Benign

0.097

Sift

Benign

0.20

.;T;T;T;T

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

1.0, 1.0

.;.;D;D;D

Vest4

0.28

MPC

0.55

ClinPred

0.026

GERP RS

0.20

Varity_R

0.11

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over