Variant chr16-85086645-G-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_001388359.1(KIAA0513):c.1012G>C(p.Glu338Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,362 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KIAA0513
NM_001388359.1 missense, splice_region

Scores

Splicing: ADA: 0.9335

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.41

Variant links:

Genes affected

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

KIAA0513 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=0.34056085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0513	NM_001388359.1 linkuse as main transcript	c.1012G>C	p.Glu338Gln	missense_variant, splice_region_variant	11/13	ENST00000683363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0513	ENST00000683363.1 linkuse as main transcript	c.1012G>C	p.Glu338Gln	missense_variant, splice_region_variant	11/13		NM_001388359.1	A1	O60268-1
KIAA0513	ENST00000566428.5 linkuse as main transcript	c.1012G>C	p.Glu338Gln	missense_variant, splice_region_variant	11/13	1		A1	O60268-1
KIAA0513	ENST00000538274.6 linkuse as main transcript	c.982G>C	p.Glu328Gln	missense_variant, splice_region_variant	10/12	2		P4	O60268-3
KIAA0513	ENST00000562564.1 linkuse as main transcript	c.118G>C	p.Glu40Gln	missense_variant, splice_region_variant	3/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461362

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 29, 2024

The c.1012G>C (p.E338Q) alteration is located in exon 11 (coding exon 10) of the KIAA0513 gene. This alteration results from a G to C substitution at nucleotide position 1012, causing the glutamic acid (E) at amino acid position 338 to be replaced by a glutamine (Q). 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

0.23

BayesDel_addAF

Benign

-0.0039

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.;T;T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D;.;D;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.33

T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.3

M;.;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.86

N;N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.054

T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T

Polyphen

0.78

P;.;P;.;.

Vest4

0.61

MutPred

0.37

Gain of methylation at K339 (P = 0.0854);.;Gain of methylation at K339 (P = 0.0854);.;.;

MVP

0.51

MPC

0.25

ClinPred

0.91

GERP RS

5.2

Varity_R

0.26

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.93

dbscSNV1_RF

Benign

0.54

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: 3

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