rs913588

Variant names:

• chr9-7174673-G-A
• rs913588
• NM_015061.6:c.3115G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-7174673-G-A
• chr9-7174673-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (14438 hom., cov: 32)
  • Exomes 𝑓: 0.48 (172626 hom.)
• Consequence: KDM4C NM_015061.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 61 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015061.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	NM_015061.6	MANE Select	c.3115G>A	p.Val1039Ile	missense	Exon 22 of 22	NP_055876.2
	KDM4C	NM_001353997.3		c.3214G>A	p.Val1072Ile	missense	Exon 23 of 23	NP_001340926.1
	KDM4C	NM_001304340.4		c.2350G>A	p.Val784Ile	missense	Exon 20 of 20	NP_001291269.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.3115G>A	p.Val1039Ile	missense	Exon 22 of 22	ENSP00000370710.3
	KDM4C	ENST00000428870.6	TSL:2	c.2176G>A	p.Val726Ile	missense	Exon 15 of 15	ENSP00000405739.2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64652 AN: 151896 Hom.: 14444 Cov.: 32

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

GnomAD2 exomes AF: 0.422 AC: 105845 AN: 251102 AF XY: 0.424

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 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.: 40 AF XY: 0.476 AC XY: 346055 AN XY: 726904

African (AFR) AF: 0.343 AC: 11480 AN: 33472

American (AMR) AF: 0.351 AC: 15704 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 9898 AN: 26128

East Asian (EAS) AF: 0.151 AC: 6003 AN: 39696

South Asian (SAS) AF: 0.364 AC: 31415 AN: 86218

European-Finnish (FIN) AF: 0.522 AC: 27870 AN: 53406

Middle Eastern (MID) AF: 0.403 AC: 2326 AN: 5768

European-Non Finnish (NFE) AF: 0.511 AC: 568388 AN: 1111360

Other (OTH) AF: 0.440 AC: 26580 AN: 60368

GnomAD4 genome AF: 0.425 AC: 64656 AN: 152014 Hom.: 14438 Cov.: 32 AF XY: 0.424 AC XY: 31507 AN XY: 74294

African (AFR) AF: 0.342 AC: 14184 AN: 41420

American (AMR) AF: 0.376 AC: 5745 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3468

East Asian (EAS) AF: 0.145 AC: 752 AN: 5172

South Asian (SAS) AF: 0.342 AC: 1644 AN: 4814

European-Finnish (FIN) AF: 0.526 AC: 5553 AN: 10566

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33994 AN: 67966

Other (OTH) AF: 0.404 AC: 855 AN: 2114

Alfa AF: 0.461 Hom.: 79496

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.20	N
PhyloP100		3.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.028
Sift	Benign	0.95	T
Sift4G	Benign	0.28	T
Polyphen		0.011	B
Vest4		0.085
MPC		0.058
ClinPred		0.012	T
GERP RS		4.7
Varity_R		0.039
gMVP		0.18
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs913588; hg19: chr9-7174673; COSMIC: COSV67184207; COSMIC: COSV67184207;