dbSNP rs147119313: KDM3A:p.Lys117Thr (chr2-86451110-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018433.6(KDM3A):c.350A>C(p.Lys117Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,450,116 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K117R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

KDM3A
NM_018433.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15809685).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3A	NM_018433.6 link	c.350A>C	p.Lys117Thr	missense_variant	Exon 4 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.350A>C	p.Lys117Thr	missense_variant	Exon 4 of 26	1	NM_018433.6	ENSP00000323659.5		Q9Y4C1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000332

AC:

AN:

241260

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

130642

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 SAS exome

AF:

0.000247

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1450116

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

721572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000494

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

.;T;T;T;T;.

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.82

T;.;.;T;.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.16

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

.;L;.;L;L;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.5

N;N;.;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.22

T;T;.;T;T;D

Sift4G

Uncertain

0.055

T;T;T;T;T;D

Polyphen

0.89

.;P;.;P;P;.

Vest4

0.51, 0.55, 0.52, 0.48

MutPred

0.41

Loss of methylation at K117 (P = 0.0106);Loss of methylation at K117 (P = 0.0106);Loss of methylation at K117 (P = 0.0106);Loss of methylation at K117 (P = 0.0106);Loss of methylation at K117 (P = 0.0106);Loss of methylation at K117 (P = 0.0106);

MVP

0.27

MPC

0.25

ClinPred

0.26

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.063

gMVP

0.49

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