Variant 5-94396252-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145678.3(KIAA0825):c.3145G>T(p.Gly1049Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,551,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

KIAA0825
NM_001145678.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0390

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04762438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0825	NM_001145678.3 linkuse as main transcript	c.3145G>T	p.Gly1049Cys	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.3145G>T	p.Gly1049Cys	missense_variant	17/21		NM_001145678.3	ENSP00000506760	A1
KIAA0825	ENST00000703867.1 linkuse as main transcript	c.3160G>T	p.Gly1054Cys	missense_variant	17/21			ENSP00000515512	P4
KIAA0825	ENST00000513200.7 linkuse as main transcript	c.3145G>T	p.Gly1049Cys	missense_variant	16/20	5		ENSP00000424618	A1	Q8IV33-1

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000363

AC:

AN:

156828

Hom.:

AF XY:

0.000386

AC XY:

AN XY:

82814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000732

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000119

Gnomad NFE exome

AF:

0.000575

Gnomad OTH exome

AF:

0.000455

GnomAD4 exome

AF:

0.000543

AC:

760

AN:

1399264

Hom.:

Cov.:

AF XY:

0.000556

AC XY:

384

AN XY:

690106

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.000561

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.000101

Gnomad4 NFE exome

AF:

0.000651

Gnomad4 OTH exome

AF:

0.000482

GnomAD4 genome

AF:

0.000585

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000579

Hom.:

Bravo

AF:

0.000661

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000160

AC:

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

Oct 22, 2021

The c.3145G>T (p.G1049C) alteration is located in exon 17 (coding exon 15) of the KIAA0825 gene. This alteration results from a G to T substitution at nucleotide position 3145, causing the glycine (G) at amino acid position 1049 to be replaced by a cysteine (C). 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

0.14

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.77

M_CAP

Benign

0.061

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.7

REVEL

Benign

0.13

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.023

Polyphen

0.99

Vest4

0.30

MVP

0.26

ClinPred

0.12

GERP RS

-3.6

Varity_R

0.17

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