Genetic Variant KDM1A:c.577+942G>A (chr1-23045428-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001009999.3(KDM1A):c.577+942G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 152,258 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.052 ( 685 hom., cov: 32)

Consequence

KDM1A
NM_001009999.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.528

Publications

2 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: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia

KDM1A links:

ENSG00000240553 (HGNC:):

ENSG00000240553 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001009999.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
KDM1A	NM_001009999.3	MANE Select	c.577+942G>A	intron	N/A	NP_001009999.1	O60341-2
KDM1A	NM_001410762.1		c.577+942G>A	intron	N/A	NP_001397691.1	A0A8I5KXU4
KDM1A	NM_001363654.2		c.518-4959G>A	intron	N/A	NP_001350583.1	R4GMQ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KDM1A	ENST00000400181.9	TSL:1 MANE Select	c.577+942G>A	intron	N/A	ENSP00000383042.5	O60341-2
KDM1A	ENST00000356634.7	TSL:1	c.518-4959G>A	intron	N/A	ENSP00000349049.3	O60341-1
KDM1A	ENST00000874661.1		c.577+942G>A	intron	N/A	ENSP00000544720.1

Frequencies

GnomAD3 genomes

AF:

0.0524

AC:

7974

AN:

152140

Hom.:

685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.0388

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0525

AC:

7991

AN:

152258

Hom.:

685

Cov.:

AF XY:

0.0513

AC XY:

3822

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.181

AC:

7510

AN:

41516

American (AMR)

AF:

0.0214

AC:

327

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000970

AC:

AN:

68030

Other (OTH)

AF:

0.0384

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

331

662

994

1325

1656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0201

Hom.:

258

Bravo

AF:

0.0592

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.8

(source)

DANN

Benign

0.45

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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