dbSNP rs2030259: KDM3A:p.Ile212Val (chr2-86456519-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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. 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 0.80 ( 48805 hom., cov: 26)

Exomes 𝑓: 0.76 ( 418859 hom. )

Consequence

KDM3A
NM_018433.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19

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 made for transcript

Verdict is Benign. Variant got -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 link	c.634A>G	p.Ile212Val	missense_variant	Exon 6 of 26	ENST00000312912.10	NP_060903.2	Q9Y4C1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM3A	ENST00000312912.10 link	c.634A>G	p.Ile212Val	missense_variant	Exon 6 of 26	1	NM_018433.6	ENSP00000323659.5		Q9Y4C1

Frequencies

GnomAD3 genomes

AF:

0.799

AC:

120608

AN:

150998

Hom.:

48743

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.765

AC:

190519

AN:

249086

Hom.:

74029

AF XY:

0.752

AC XY:

101251

AN XY:

134716

show subpopulations

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 SAS exome

AF:

0.581

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.:

AF XY:

0.749

AC XY:

542754

AN XY:

724298

show subpopulations

Gnomad4 AFR exome

AF:

0.909

Gnomad4 AMR exome

AF:

0.769

Gnomad4 ASJ exome

AF:

0.731

Gnomad4 EAS exome

AF:

0.956

Gnomad4 SAS exome

AF:

0.586

Gnomad4 FIN exome

AF:

0.791

Gnomad4 NFE exome

AF:

0.755

Gnomad4 OTH exome

AF:

0.759

GnomAD4 genome

AF:

0.799

AC:

120726

AN:

151110

Hom.:

48805

Cov.:

AF XY:

0.794

AC XY:

58595

AN XY:

73758

show subpopulations

Gnomad4 AFR

AF:

0.900

Gnomad4 AMR

AF:

0.736

Gnomad4 ASJ

AF:

0.727

Gnomad4 EAS

AF:

0.955

Gnomad4 SAS

AF:

0.590

Gnomad4 FIN

AF:

0.784

Gnomad4 NFE

AF:

0.762

Gnomad4 OTH

AF:

0.750

Alfa

AF:

0.765

Hom.:

112272

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

BayesDel_noAF

Benign

-0.61

CADD

Benign

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

LIST_S2

Benign

0.22

.;.;T;.

MetaRNN

Benign

5.5e-7

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.97

N;.;N;N

PrimateAI

Uncertain

0.49

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

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.016

gMVP

0.14

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over