Genetic Variant KDM3A:p.Ile212Leu (chr2-86456519-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018433.6(KDM3A):c.634A>T(p.Ile212Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KDM3A
NM_018433.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19

Publications

34 publications found

Variant links:

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]

KDM3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11468893).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018433.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM3A	NM_018433.6	MANE Select	c.634A>T	p.Ile212Leu	missense	Exon 6 of 26	NP_060903.2
	KDM3A	NM_001146688.2		c.634A>T	p.Ile212Leu	missense	Exon 6 of 26	NP_001140160.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KDM3A	ENST00000312912.10	TSL:1 MANE Select	c.634A>T	p.Ile212Leu	missense	Exon 6 of 26	ENSP00000323659.5
KDM3A	ENST00000409064.5	TSL:1	c.634A>T	p.Ile212Leu	missense	Exon 6 of 26	ENSP00000386516.1
KDM3A	ENST00000900202.1		c.634A>T	p.Ile212Leu	missense	Exon 6 of 26	ENSP00000570261.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457432

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725220

African (AFR)

AF:

0.00

AC:

AN:

33254

American (AMR)

AF:

0.00

AC:

AN:

44310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39520

South Asian (SAS)

AF:

0.00

AC:

AN:

85818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109326

Other (OTH)

AF:

0.00

AC:

AN:

60202

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

158703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.042

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.54

M_CAP

Benign

0.015

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.42

REVEL

Benign

0.059

Sift

Uncertain

0.016

Sift4G

Benign

0.27

Polyphen

0.0010

Vest4

0.27

MutPred

0.21

Gain of disorder (P = 0.1391)

MVP

0.15

MPC

0.11

ClinPred

0.22

GERP RS

3.5

Varity_R

0.068

gMVP

0.32

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over