Variant 5-94396384-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001145678.3(KIAA0825):c.3013T>A(p.Phe1005Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,550,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

KIAA0825
NM_001145678.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.29

Variant links:

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

KIAA0825 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008657545).

BP6

Variant 5-94396384-A-T is Benign according to our data. Variant chr5-94396384-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041143.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0825	NM_001145678.3 linkuse as main transcript	c.3013T>A	p.Phe1005Ile	missense_variant	17/21	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1 linkuse as main transcript	c.3013T>A	p.Phe1005Ile	missense_variant	17/21		NM_001145678.3	ENSP00000506760	A1
KIAA0825	ENST00000703867.1 linkuse as main transcript	c.3028T>A	p.Phe1010Ile	missense_variant	17/21			ENSP00000515512	P4
KIAA0825	ENST00000513200.7 linkuse as main transcript	c.3013T>A	p.Phe1005Ile	missense_variant	16/20	5		ENSP00000424618	A1	Q8IV33-1

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00105

AC:

160

AN:

152872

Hom.:

AF XY:

0.00117

AC XY:

AN XY:

81006

show subpopulations

Gnomad AFR exome

AF:

0.000255

Gnomad AMR exome

AF:

0.00319

Gnomad ASJ exome

AF:

0.00275

Gnomad EAS exome

AF:

0.00185

Gnomad SAS exome

AF:

0.000407

Gnomad FIN exome

AF:

0.000862

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.000234

GnomAD4 exome

AF:

0.000370

AC:

517

AN:

1398074

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

285

AN XY:

689460

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.00311

Gnomad4 ASJ exome

AF:

0.00219

Gnomad4 EAS exome

AF:

0.00151

Gnomad4 SAS exome

AF:

0.000355

Gnomad4 FIN exome

AF:

0.000650

Gnomad4 NFE exome

AF:

0.000193

Gnomad4 OTH exome

AF:

0.000449

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152234

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000437

Hom.:

Bravo

AF:

0.00105

ExAC

AF:

0.000588

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIAA0825-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 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

0.082

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0057

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

M_CAP

Benign

0.011

MetaRNN

Benign

0.0087

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.41

REVEL

Benign

0.11

Sift

Benign

0.075

Sift4G

Uncertain

0.039

Polyphen

0.62

Vest4

0.38

MVP

0.28

ClinPred

0.040

GERP RS

5.3

Varity_R

0.12

Splicing

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