dbSNP rs1341012672: KDM1A:p.Gly20Arg (chr1-23019654-G-A) – 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>A(p.Gly20Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. G20G) has been classified as Likely benign.

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

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

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:

Genome browser will be placed here

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=0.3779312).

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>A	p.Gly20Arg	missense	Exon 1 of 21	NP_001009999.1	O60341-2
KDM1A	NM_001410762.1		c.58G>A	p.Gly20Arg	missense	Exon 1 of 20	NP_001397691.1	A0A8I5KXU4
KDM1A	NM_001363654.2		c.58G>A	p.Gly20Arg	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>A	p.Gly20Arg	missense	Exon 1 of 21	ENSP00000383042.5	O60341-2
KDM1A	ENST00000356634.7	TSL:1	c.58G>A	p.Gly20Arg	missense	Exon 1 of 19	ENSP00000349049.3	O60341-1
KDM1A	ENST00000874661.1		c.58G>A	p.Gly20Arg	missense	Exon 1 of 21	ENSP00000544720.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1255652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

616524

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:

59840

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.55

PhyloP100

3.8

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.54

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.28

MutPred

0.20

Gain of methylation at G20 (P = 0.0062)

MVP

0.52

MPC

1.4

ClinPred

0.88

GERP RS

3.4

PromoterAI

-0.0058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.29

Mutation Taster

=96/4

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