dbSNP rs913588: KDM4C:p.Val1039Ile (chr9-7174673-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015061.6(KDM4C):c.3115G>A(p.Val1039Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,613,154 control chromosomes in the GnomAD database, including 187,064 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.43 ( 14438 hom., cov: 32)

Exomes 𝑓: 0.48 ( 172626 hom. )

Consequence

KDM4C
NM_015061.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.15

Variant links:

Genes affected

KDM4C (HGNC:17071): (lysine demethylase 4C) This gene is a member of the Jumonji domain 2 (JMJD2) family. The encoded protein is a trimethylation-specific demethylase, and converts specific trimethylated histone residues to the dimethylated form. This enzymatic action regulates gene expression and chromosome segregation. Chromosomal aberrations and changes in expression of this gene may be found in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

KDM4C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001106441).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6 link	c.3115G>A	p.Val1039Ile	missense_variant	Exon 22 of 22	ENST00000381309.8	NP_055876.2	Q9H3R0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8 link	c.3115G>A	p.Val1039Ile	missense_variant	Exon 22 of 22	1	NM_015061.6	ENSP00000370710.3		Q9H3R0-1
KDM4C	ENST00000428870.6 link	c.2176G>A	p.Val726Ile	missense_variant	Exon 15 of 15	2		ENSP00000405739.2		C9J879

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64652

AN:

151896

Hom.:

14444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.529

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.409

GnomAD3 exomes

AF:

0.422

AC:

105845

AN:

251102

Hom.:

23708

AF XY:

0.424

AC XY:

57576

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.346

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.164

Gnomad SAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.526

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.441

GnomAD4 exome

AF:

0.479

AC:

699664

AN:

1461140

Hom.:

172626

Cov.:

AF XY:

0.476

AC XY:

346055

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.343

Gnomad4 AMR exome

AF:

0.351

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.364

Gnomad4 FIN exome

AF:

0.522

Gnomad4 NFE exome

AF:

0.511

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.425

AC:

64656

AN:

152014

Hom.:

14438

Cov.:

AF XY:

0.424

AC XY:

31507

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.376

Gnomad4 ASJ

AF:

0.380

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.526

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.404

Alfa

AF:

0.465

Hom.:

41461

Bravo

AF:

0.411

TwinsUK

AF:

0.530

AC:

1967

ALSPAC

AF:

0.521

AC:

2007

ESP6500AA

AF:

0.351

AC:

1546

ESP6500EA

AF:

0.498

AC:

4279

ExAC

AF:

0.422

AC:

51294

Asia WGS

AF:

0.234

AC:

815

AN:

3478

EpiCase

AF:

0.483

EpiControl

AF:

0.484

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0043

T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

N;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.020

N;N

REVEL

Benign

0.028

Sift

Benign

0.95

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.011

B;.

Vest4

0.085

MPC

0.058

ClinPred

0.012

GERP RS

4.7

Varity_R

0.039

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over