Variant 6-24596250-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000378214.8(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. 14/20 in silico tools predict a benign outcome for this variant. 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 0.91 ( 63527 hom., cov: 33)

Exomes 𝑓: 0.91 ( 601419 hom. )

Consequence

KIAA0319
ENST00000378214.8 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.800

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4 linkuse as main transcript	c.424A>C	p.Thr142Pro	missense_variant	3/21	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.424A>C	p.Thr142Pro	missense_variant	3/21	1	NM_014809.4	ENSP00000367459	P2	Q5VV43-1
KIAA0319	ENST00000537886.5 linkuse as main transcript	c.424A>C	p.Thr142Pro	missense_variant	3/19	1		ENSP00000439700		Q5VV43-4
KIAA0319	ENST00000535378.5 linkuse as main transcript	c.397A>C	p.Thr133Pro	missense_variant	4/22	2		ENSP00000442403	A2	Q5VV43-2
KIAA0319	ENST00000430948.6 linkuse as main transcript	c.289A>C	p.Thr97Pro	missense_variant	2/20	2		ENSP00000401086	A2	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

GnomAD3 exomes

AF:

0.918

AC:

230511

AN:

251126

Hom.:

105966

AF XY:

0.916

AC XY:

124385

AN XY:

135788

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 SAS exome

AF:

0.934

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

Gnomad4 AFR exome

AF:

0.924

Gnomad4 AMR exome

AF:

0.950

Gnomad4 ASJ exome

AF:

0.910

Gnomad4 EAS exome

AF:

0.977

Gnomad4 SAS exome

AF:

0.936

Gnomad4 FIN exome

AF:

0.906

Gnomad4 NFE exome

AF:

0.900

Gnomad4 OTH exome

AF:

0.914

GnomAD4 genome

AF:

0.913

AC:

139022

AN:

152262

Hom.:

63527

Cov.:

AF XY:

0.916

AC XY:

68193

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.926

Gnomad4 AMR

AF:

0.935

Gnomad4 ASJ

AF:

0.917

Gnomad4 EAS

AF:

0.986

Gnomad4 SAS

AF:

0.936

Gnomad4 FIN

AF:

0.918

Gnomad4 NFE

AF:

0.894

Gnomad4 OTH

AF:

0.909

Alfa

AF:

0.898

Hom.:

150665

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

0.035

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.68

CADD

Benign

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

MutationTaster

Benign

1.0

P;P;P;P;P

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

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

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