chr2-86456519-A-G

Variant names:

• chr2-86456519-A-G
• rs2030259
• NM_018433.6:c.634A>G

Variant summary

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

The NM_018433.6(KDM3A):​c.634A>G​(p.Ile212Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,606,618 control chromosomes in the GnomAD database, including 467,664 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 0.80 (48805 hom., cov: 26)
  • Exomes 𝑓: 0.76 (418859 hom.)
• Consequence: KDM3A NM_018433.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 34 publications found

Genes affected

KDM3A (HGNC:20815): (lysine demethylase 3A) Enables androgen receptor binding activity; histone H3-methyl-lysine-9 demethylase activity; and iron ion binding activity. Involved in several processes, including androgen receptor signaling pathway; formaldehyde biosynthetic process; and histone H3-K9 demethylation. Located in nucleoplasm. Implicated in cervical cancer and colon cancer. Biomarker of Ewing sarcoma; hepatocellular carcinoma; nasopharynx carcinoma; and prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.4812926E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3A	NM_018433.6	c.634A>G	p.Ile212Val	missense_variant	Exon 6 of 26	ENST00000312912.10	NP_060903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM3A	ENST00000312912.10	c.634A>G	p.Ile212Val	missense_variant	Exon 6 of 26	1	NM_018433.6	ENSP00000323659.5

Frequencies

GnomAD3 genomes AF: 0.799 AC: 120608 AN: 150998 Hom.: 48743 Cov.: 26

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.749

GnomAD2 exomes AF: 0.765 AC: 190519 AN: 249086 AF XY: 0.752

Gnomad AFR exome AF: 0.906

Gnomad AMR exome AF: 0.774

Gnomad ASJ exome AF: 0.728

Gnomad EAS exome AF: 0.956

Gnomad FIN exome AF: 0.788

Gnomad NFE exome AF: 0.760

Gnomad OTH exome AF: 0.756

GnomAD4 exome AF: 0.756 AC: 1099718 AN: 1455508 Hom.: 418859 Cov.: 34 AF XY: 0.749 AC XY: 542754 AN XY: 724298

African (AFR) AF: 0.909 AC: 30205 AN: 33230

American (AMR) AF: 0.769 AC: 33962 AN: 44168

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 19048 AN: 26042

East Asian (EAS) AF: 0.956 AC: 37758 AN: 39512

South Asian (SAS) AF: 0.586 AC: 50197 AN: 85620

European-Finnish (FIN) AF: 0.791 AC: 42208 AN: 53354

Middle Eastern (MID) AF: 0.722 AC: 4012 AN: 5560

European-Non Finnish (NFE) AF: 0.755 AC: 836693 AN: 1107886

Other (OTH) AF: 0.759 AC: 45635 AN: 60136

GnomAD4 genome AF: 0.799 AC: 120726 AN: 151110 Hom.: 48805 Cov.: 26 AF XY: 0.794 AC XY: 58595 AN XY: 73758

African (AFR) AF: 0.900 AC: 37068 AN: 41192

American (AMR) AF: 0.736 AC: 11156 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2525 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4905 AN: 5136

South Asian (SAS) AF: 0.590 AC: 2828 AN: 4790

European-Finnish (FIN) AF: 0.784 AC: 8033 AN: 10240

Middle Eastern (MID) AF: 0.715 AC: 206 AN: 288

European-Non Finnish (NFE) AF: 0.762 AC: 51715 AN: 67834

Other (OTH) AF: 0.750 AC: 1571 AN: 2094

Alfa AF: 0.772 Hom.: 158703

Bravo AF: 0.807

TwinsUK AF: 0.749 AC: 2777

ALSPAC AF: 0.754 AC: 2907

ESP6500AA AF: 0.897 AC: 3952

ESP6500EA AF: 0.753 AC: 6476

ExAC AF: 0.766 AC: 92979

Asia WGS AF: 0.784 AC: 2719 AN: 3470

EpiCase AF: 0.752

EpiControl AF: 0.751

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.80
DEOGEN2	Benign	0.017	T;T;T;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.22	.;.;T;.
MetaRNN	Benign	5.5e-7	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.97	N;.;N;N
PhyloP100		2.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.31	N;.;N;N
REVEL	Benign	0.055
Sift	Benign	0.86	T;.;T;T
Sift4G	Benign	0.79	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.057
MPC		0.092
ClinPred		0.0024	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.016
gMVP		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2030259; hg19: chr2-86683642; COSMIC: COSV107360184; COSMIC: COSV107360184;