Variant 4-6824501-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_014743.3(KIAA0232):c.48C>G(p.Ser16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,614,166 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 5 hom. )

Consequence

KIAA0232
NM_014743.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.48

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005654782).

BP6

Variant 4-6824501-C-G is Benign according to our data. Variant chr4-6824501-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3052068.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0232	NM_014743.3 linkuse as main transcript	c.48C>G	p.Ser16Arg	missense_variant	3/10	ENST00000307659.6	NP_055558.2	Q92628A5YKK5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIAA0232	ENST00000307659.6 linkuse as main transcript	c.48C>G	p.Ser16Arg	missense_variant	3/10	1	NM_014743.3	ENSP00000303928.5	Q92628
KIAA0232	ENST00000425103.5 linkuse as main transcript	c.48C>G	p.Ser16Arg	missense_variant	2/9	1		ENSP00000413739.1	Q92628
KIAA0232	ENST00000508423.1 linkuse as main transcript	c.48C>G	p.Ser16Arg	missense_variant	2/2	2		ENSP00000426815.1	D6REK0

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

194

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

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:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00232

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00198

AC:

494

AN:

249542

Hom.:

AF XY:

0.00200

AC XY:

271

AN XY:

135386

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.00195

AC:

2856

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

1365

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00243

Gnomad4 NFE exome

AF:

0.00233

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00127

AC:

194

AN:

152296

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00232

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00220

Hom.:

Bravo

AF:

0.00116

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000774

AC:

ESP6500EA

AF:

0.00266

AC:

ExAC

AF:

0.00252

AC:

305

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIAA0232-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 07, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

.;T;T

Eigen

Benign

-0.063

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;T;.

M_CAP

Benign

0.0047

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;L;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.16

T;D;D

Sift4G

Benign

0.11

T;T;T

Polyphen

0.051

.;B;B

Vest4

0.20

MutPred

0.27

Gain of glycosylation at Y21 (P = 0.0136);Gain of glycosylation at Y21 (P = 0.0136);Gain of glycosylation at Y21 (P = 0.0136);

MVP

0.043

MPC

0.58

ClinPred

0.019

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.30

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