Variant 5-94386331-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001145678.3(KIAA0825):c.3530C>T(p.Thr1177Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0332 in 1,551,332 control chromosomes in the GnomAD database, including 1,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.026 ( 77 hom., cov: 32)

Exomes 𝑓: 0.034 ( 943 hom. )

Consequence

KIAA0825
NM_001145678.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0540

Variant links:

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

KIAA0825 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011944175).

BP6

Variant 5-94386331-G-A is Benign according to our data. Variant chr5-94386331-G-A is described in ClinVar as [Benign]. Clinvar id is 3059786.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0825	NM_001145678.3 linkuse as main transcript	c.3530C>T	p.Thr1177Met	missense_variant	19/21	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.3530C>T	p.Thr1177Met	missense_variant	19/21		NM_001145678.3	ENSP00000506760	A1
KIAA0825	ENST00000703867.1 linkuse as main transcript	c.3545C>T	p.Thr1182Met	missense_variant	19/21			ENSP00000515512	P4
KIAA0825	ENST00000513200.7 linkuse as main transcript	c.3530C>T	p.Thr1177Met	missense_variant	18/20	5		ENSP00000424618	A1	Q8IV33-1

Frequencies

GnomAD3 genomes

AF:

0.0263

AC:

4004

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00729

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0216

Gnomad ASJ

AF:

0.0433

Gnomad EAS

AF:

0.0616

Gnomad SAS

AF:

0.0508

Gnomad FIN

AF:

0.0372

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0324

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0351

AC:

5530

AN:

157762

Hom.:

124

AF XY:

0.0367

AC XY:

3054

AN XY:

83290

show subpopulations

Gnomad AFR exome

AF:

0.00562

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0419

Gnomad EAS exome

AF:

0.0657

Gnomad SAS exome

AF:

0.0484

Gnomad FIN exome

AF:

0.0451

Gnomad NFE exome

AF:

0.0332

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0340

AC:

47551

AN:

1399140

Hom.:

943

Cov.:

AF XY:

0.0346

AC XY:

23864

AN XY:

690076

show subpopulations

Gnomad4 AFR exome

AF:

0.00510

Gnomad4 AMR exome

AF:

0.0153

Gnomad4 ASJ exome

AF:

0.0445

Gnomad4 EAS exome

AF:

0.0579

Gnomad4 SAS exome

AF:

0.0482

Gnomad4 FIN exome

AF:

0.0435

Gnomad4 NFE exome

AF:

0.0329

Gnomad4 OTH exome

AF:

0.0348

GnomAD4 genome

AF:

0.0263

AC:

4006

AN:

152192

Hom.:

Cov.:

AF XY:

0.0268

AC XY:

1995

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00727

Gnomad4 AMR

AF:

0.0215

Gnomad4 ASJ

AF:

0.0433

Gnomad4 EAS

AF:

0.0605

Gnomad4 SAS

AF:

0.0512

Gnomad4 FIN

AF:

0.0372

Gnomad4 NFE

AF:

0.0324

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.0335

Hom.:

187

Bravo

AF:

0.0230

TwinsUK

AF:

0.0272

AC:

101

ALSPAC

AF:

0.0368

AC:

142

ExAC

AF:

0.0372

AC:

930

Asia WGS

AF:

0.0920

AC:

320

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIAA0825-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2019

This variant is classified as 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

0.063

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.74

DANN

Benign

0.95

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0012

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.090

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.46

REVEL

Benign

0.022

Sift

Benign

0.16

Sift4G

Benign

0.25

Polyphen

0.014

Vest4

0.019

ClinPred

0.0033

GERP RS

-3.6

Varity_R

0.024

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