Genetic Variant KDM1A:p.Gly20Trp (chr1-23019654-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001009999.3(KDM1A):c.58G>T(p.Gly20Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. G20R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KDM1A
NM_001009999.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.84

Publications

0 publications found

Variant links:

Genes affected

KDM1A (HGNC:29079): (lysine demethylase 1A) This gene encodes a nuclear protein containing a SWIRM domain, a FAD-binding motif, and an amine oxidase domain. This protein is a component of several histone deacetylase complexes, though it silences genes by functioning as a histone demethylase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

KDM1A Gene-Disease associations (from GenCC):

palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

KDM1A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4174964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009999.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM1A	NM_001009999.3	MANE Select	c.58G>T	p.Gly20Trp	missense	Exon 1 of 21	NP_001009999.1	O60341-2
KDM1A	NM_001410762.1		c.58G>T	p.Gly20Trp	missense	Exon 1 of 20	NP_001397691.1	A0A8I5KXU4
KDM1A	NM_001363654.2		c.58G>T	p.Gly20Trp	missense	Exon 1 of 19	NP_001350583.1	R4GMQ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM1A	ENST00000400181.9	TSL:1 MANE Select	c.58G>T	p.Gly20Trp	missense	Exon 1 of 21	ENSP00000383042.5	O60341-2
KDM1A	ENST00000356634.7	TSL:1	c.58G>T	p.Gly20Trp	missense	Exon 1 of 19	ENSP00000349049.3	O60341-1
KDM1A	ENST00000874661.1		c.58G>T	p.Gly20Trp	missense	Exon 1 of 21	ENSP00000544720.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

43880

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1255650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

616522

African (AFR)

AF:

0.00

AC:

AN:

25102

American (AMR)

AF:

0.00

AC:

AN:

16046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19706

East Asian (EAS)

AF:

0.00

AC:

AN:

28428

South Asian (SAS)

AF:

0.00

AC:

AN:

59838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3618

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1019930

Other (OTH)

AF:

0.00

AC:

AN:

51522

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.55

PhyloP100

3.8

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.76

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.36

MutPred

0.19

Loss of phosphorylation at T21 (P = 0.0964)

MVP

0.68

MPC

2.0

ClinPred

0.91

GERP RS

3.4

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.28

Mutation Taster

=97/3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over