Variant 16-27210412-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024773.3(KDM8):c.289A>G(p.Ile97Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00816 in 1,608,426 control chromosomes in the GnomAD database, including 81 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 (★★).

Frequency

Genomes: 𝑓 0.0057 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0084 ( 78 hom. )

Consequence

KDM8
NM_024773.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.31

Variant links:

Genes affected

KDM8 (HGNC:25840): (lysine demethylase 8) This gene likely encodes a histone lysine demethylase. Studies of a similar protein in mouse indicate a potential role for this protein as a tumor suppressor. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2009]

KDM8 links:

KDM8 (HGNC:):

KDM8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006112933).

BP6

Variant 16-27210412-A-G is Benign according to our data. Variant chr16-27210412-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 710277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM8	NM_024773.3 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	2/8	ENST00000286096.9	NP_079049.2	Q8N371-1A0A0S2Z5T1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM8	ENST00000286096.9 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	2/8	1	NM_024773.3	ENSP00000286096.5		Q8N371-1

Frequencies

GnomAD3 genomes

AF:

0.00566

AC:

861

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00927

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00539

AC:

1343

AN:

249136

Hom.:

AF XY:

0.00544

AC XY:

734

AN XY:

135046

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.000704

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000883

Gnomad FIN exome

AF:

0.0100

Gnomad NFE exome

AF:

0.00850

Gnomad OTH exome

AF:

0.00706

GnomAD4 exome

AF:

0.00843

AC:

12269

AN:

1456088

Hom.:

Cov.:

AF XY:

0.00811

AC XY:

5867

AN XY:

723174

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.000729

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.00988

Gnomad4 OTH exome

AF:

0.00787

GnomAD4 genome

AF:

0.00565

AC:

861

AN:

152338

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00300

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.00928

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00800

Hom.:

Bravo

AF:

0.00483

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.00828

AC:

ExAC

AF:

0.00546

AC:

663

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00791

EpiControl

AF:

0.00954

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 26, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.029

T;T;.;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

T;T;T;T;T

MetaRNN

Benign

0.0061

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.55

N;.;.;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.24

N;N;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.049

D;D;T;D;D

Sift4G

Benign

0.20

T;T;T;D;D

Polyphen

0.0

B;.;B;.;B

Vest4

0.13

MVP

0.25

MPC

0.15

ClinPred

0.0046

GERP RS

3.4

Varity_R

0.046

gMVP

0.16

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