Genetic Variant NM_001009999.3:c.31G>A (chr1-23019627-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001009999.3(KDM1A):c.31G>A(p.Ala11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000847 in 1,416,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

KDM1A
NM_001009999.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0901818).

BS2

High AC in GnomAdExome4 at 10 AD gene.

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.31G>A	p.Ala11Thr	missense	Exon 1 of 21	NP_001009999.1	O60341-2
KDM1A	NM_001410762.1		c.31G>A	p.Ala11Thr	missense	Exon 1 of 20	NP_001397691.1	A0A8I5KXU4
KDM1A	NM_001363654.2		c.31G>A	p.Ala11Thr	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.31G>A	p.Ala11Thr	missense	Exon 1 of 21	ENSP00000383042.5	O60341-2
KDM1A	ENST00000356634.7	TSL:1	c.31G>A	p.Ala11Thr	missense	Exon 1 of 19	ENSP00000349049.3	O60341-1
KDM1A	ENST00000874661.1		c.31G>A	p.Ala11Thr	missense	Exon 1 of 21	ENSP00000544720.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000184

AC:

AN:

54434

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000380

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000790

AC:

AN:

1265148

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

622308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25420

American (AMR)

AF:

0.00

AC:

AN:

16860

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19760

East Asian (EAS)

AF:

0.000136

AC:

AN:

29396

South Asian (SAS)

AF:

0.0000826

AC:

AN:

60520

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3562

European-Non Finnish (NFE)

AF:

9.74e-7

AC:

AN:

1026472

Other (OTH)

AF:

0.00

AC:

AN:

51826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

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

AF:

0.0000132

AC:

AN:

151776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67930

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000193

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.6

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.24

REVEL

Benign

0.057

Sift

Pathogenic

0.0

Sift4G

Benign

0.26

Polyphen

0.81

Vest4

0.34

MutPred

0.36

Gain of glycosylation at A11 (P = 0.0029)

MVP

0.35

MPC

1.1

ClinPred

0.50

GERP RS

4.3

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.35

gMVP

0.37

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over