1-23019623-C-CGCG

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001009999.3(KDM1A):​c.39_41dupGGC​(p.Ala14dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 1,418,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

KDM1A
NM_001009999.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.53
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6
Variant 1-23019623-C-CGCG is Benign according to our data. Variant chr1-23019623-C-CGCG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1675352.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KDM1ANM_001009999.3 linkc.39_41dupGGC p.Ala14dup disruptive_inframe_insertion Exon 1 of 21 ENST00000400181.9 NP_001009999.1 O60341-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KDM1AENST00000400181.9 linkc.39_41dupGGC p.Ala14dup disruptive_inframe_insertion Exon 1 of 21 1 NM_001009999.3 ENSP00000383042.5 O60341-2

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151712
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000265
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000480
GnomAD4 exome
AF:
0.0000395
AC:
50
AN:
1266376
Hom.:
0
Cov.:
31
AF XY:
0.0000369
AC XY:
23
AN XY:
623036
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000116
Gnomad4 ASJ exome
AF:
0.0000507
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000331
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000389
Gnomad4 OTH exome
AF:
0.0000965
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
151712
Hom.:
0
Cov.:
32
AF XY:
0.0000405
AC XY:
3
AN XY:
74086
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000265
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000480
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000642

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2022KDM1A: BP3 -
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 11, 2024This variant, c.39_41dup, results in the insertion of 1 amino acid(s) of the KDM1A protein (p.Ala18dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with KDM1A-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs765476443; hg19: chr1-23346116; API