Variant chr6-24551440-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014809.4(KIAA0319):c.3034A>G(p.Lys1012Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,454,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

KIAA0319
NM_014809.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37285838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4 linkuse as main transcript	c.3034A>G	p.Lys1012Glu	missense_variant	20/21	ENST00000378214.8	NP_055624.2	Q5VV43-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8 linkuse as main transcript	c.3034A>G	p.Lys1012Glu	missense_variant	20/21	1	NM_014809.4	ENSP00000367459.3		Q5VV43-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454832

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724336

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.3034A>G (p.K1012E) alteration is located in exon 20 (coding exon 19) of the KIAA0319 gene. This alteration results from a A to G substitution at nucleotide position 3034, causing the lysine (K) at amino acid position 1012 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0063

.;.;.;T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

T;T;T;.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.37

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;.;.;M;M

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.8

.;N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0080

.;D;D;D;D

Sift4G

Uncertain

0.029

D;D;D;D;D

Polyphen

1.0, 1.0

.;.;D;D;D

Vest4

0.18

MutPred

0.19

.;.;.;Loss of ubiquitination at K1012 (P = 0.0023);Loss of ubiquitination at K1012 (P = 0.0023);

MVP

0.48

MPC

0.21

ClinPred

0.84

GERP RS

2.0

Varity_R

0.19

gMVP

0.47

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over