Variant 16-85077535-C-T 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.685C>T(p.Arg229Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,614,166 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 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

KIAA0513
NM_001388359.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14480615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0513	NM_001388359.1 linkuse as main transcript	c.685C>T	p.Arg229Trp	missense_variant	6/13	ENST00000683363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0513	ENST00000683363.1 linkuse as main transcript	c.685C>T	p.Arg229Trp	missense_variant	6/13		NM_001388359.1	A1	O60268-1
KIAA0513	ENST00000566428.5 linkuse as main transcript	c.685C>T	p.Arg229Trp	missense_variant	6/13	1		A1	O60268-1
KIAA0513	ENST00000567328.6 linkuse as main transcript	c.685C>T	p.Arg229Trp	missense_variant	6/8	1			O60268-2
KIAA0513	ENST00000538274.6 linkuse as main transcript	c.685C>T	p.Arg229Trp	missense_variant	6/12	2		P4	O60268-3

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

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:

0.000367

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000227

AC:

AN:

251092

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000409

AC:

598

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

283

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000493

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000256

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000350

Hom.:

Bravo

AF:

0.000321

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000533

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

Jul 13, 2021

The c.685C>T (p.R229W) alteration is located in exon 6 (coding exon 5) of the KIAA0513 gene. This alteration results from a C to T substitution at nucleotide position 685, causing the arginine (R) at amino acid position 229 to be replaced by a tryptophan (W). 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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Pathogenic

0.19

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.079

T;.;T;.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.99

D;D;.;D;D

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.6

M;M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.5

D;N;D;D;N

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

D;.;D;.;.

Vest4

0.87

MVP

0.67

MPC

0.46

ClinPred

0.21

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.65

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