Variant 16-85067324-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388359.1(KIAA0513):c.253G>A(p.Glu85Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,610,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

KIAA0513
NM_001388359.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

KIAA0513 (HGNC:29058): (KIAA0513) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

KIAA0513 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12681752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0513	NM_001388359.1 linkuse as main transcript	c.253G>A	p.Glu85Lys	missense_variant	2/13	ENST00000683363.1	NP_001375288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0513	ENST00000683363.1 linkuse as main transcript	c.253G>A	p.Glu85Lys	missense_variant	2/13		NM_001388359.1	ENSP00000507772	A1	O60268-1
KIAA0513	ENST00000566428.5 linkuse as main transcript	c.253G>A	p.Glu85Lys	missense_variant	2/13	1		ENSP00000457408	A1	O60268-1
KIAA0513	ENST00000567328.6 linkuse as main transcript	c.253G>A	p.Glu85Lys	missense_variant	2/8	1		ENSP00000455544		O60268-2
KIAA0513	ENST00000538274.6 linkuse as main transcript	c.253G>A	p.Glu85Lys	missense_variant	2/12	2		ENSP00000446439	P4	O60268-3

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000390

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000524

AC:

AN:

248282

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134674

show subpopulations

Gnomad AFR exome

AF:

0.000560

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000507

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1459760

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726274

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000106

AC:

AN:

151086

Hom.:

Cov.:

AF XY:

0.0000813

AC XY:

AN XY:

73782

show subpopulations

Gnomad4 AFR

AF:

0.000390

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

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

Dec 12, 2023

The c.253G>A (p.E85K) alteration is located in exon 2 (coding exon 1) of the KIAA0513 gene. This alteration results from a G to A substitution at nucleotide position 253, causing the glutamic acid (E) at amino acid position 85 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

T;.;T;.

Eigen

Benign

-0.050

Eigen_PC

Benign

-0.060

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;.;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;M;M;M

MutationTaster

Benign

0.83

D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.073

Sift

Benign

0.11

T;T;T;D

Sift4G

Benign

0.35

T;T;T;T

Polyphen

0.56

P;.;P;.

Vest4

0.26

MVP

0.41

MPC

0.12

ClinPred

0.059

GERP RS

3.7

Varity_R

0.12

gMVP

0.29

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

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