dbSNP rs1006417228: KDM3A:p.Val175Met (chr2-86455154-G-A) – 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.523G>A(p.Val175Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V175L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KDM3A
NM_018433.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

0 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=0.18525025).

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.523G>A	p.Val175Met	missense	Exon 5 of 26	NP_060903.2
	KDM3A	NM_001146688.2		c.523G>A	p.Val175Met	missense	Exon 5 of 26	NP_001140160.1	Q9Y4C1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM3A	ENST00000312912.10	TSL:1 MANE Select	c.523G>A	p.Val175Met	missense	Exon 5 of 26	ENSP00000323659.5	Q9Y4C1
KDM3A	ENST00000409064.5	TSL:1	c.523G>A	p.Val175Met	missense	Exon 5 of 26	ENSP00000386516.1	Q9Y4C1
KDM3A	ENST00000900202.1		c.523G>A	p.Val175Met	missense	Exon 5 of 26	ENSP00000570261.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246114

AF XY:

0.00000750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453324

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32922

American (AMR)

AF:

0.00

AC:

AN:

43256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39408

South Asian (SAS)

AF:

0.00

AC:

AN:

85264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1107358

Other (OTH)

AF:

0.00

AC:

AN:

60068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

0.084

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.80

M_CAP

Benign

0.016

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

PhyloP100

1.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.13

REVEL

Benign

0.058

Sift

Benign

0.048

Sift4G

Benign

0.074

Polyphen

0.87

Vest4

0.32

MutPred

0.21

Loss of methylation at K176 (P = 0.0172)

MVP

0.28

MPC

0.11

ClinPred

0.29

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.24

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over