Variant 4-6861365-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014743.3(KIAA0232):c.983G>A(p.Arg328Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

KIAA0232
NM_014743.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.77

Variant links:

Genes affected

KIAA0232 (HGNC:28992): (KIAA0232) Predicted to enable ATP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

KIAA0232 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0232	NM_014743.3 linkuse as main transcript	c.983G>A	p.Arg328Gln	missense_variant	7/10	ENST00000307659.6	NP_055558.2	Q92628A5YKK5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0232	ENST00000307659.6 linkuse as main transcript	c.983G>A	p.Arg328Gln	missense_variant	7/10	1	NM_014743.3	ENSP00000303928.5		Q92628
KIAA0232	ENST00000425103.5 linkuse as main transcript	c.983G>A	p.Arg328Gln	missense_variant	6/9	1		ENSP00000413739.1		Q92628

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

248992

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.00

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:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000951

AC:

139

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000935

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

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:

0.000115

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00000827

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Apr 25, 2023

The c.983G>A (p.R328Q) alteration is located in exon 7 (coding exon 5) of the KIAA0232 gene. This alteration results from a G to A substitution at nucleotide position 983, causing the arginine (R) at amino acid position 328 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

0.10

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.048

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;.

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.9

L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.035

D;D

Polyphen

0.99

D;D

Vest4

0.65

MVP

0.20

MPC

0.71

ClinPred

0.77

GERP RS

5.0

Varity_R

0.11

gMVP

0.17

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