1-23019623-C-CGCG

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001009999.3(KDM1A):c.39_41dup(p.Ala17dup) variant causes a 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 inframe_insertion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.53

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]

ACMG classification

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 GnomAd at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM1A	NM_001009999.3	c.39_41dup	p.Ala17dup	inframe_insertion	1/21	ENST00000400181.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM1A	ENST00000400181.9	c.39_41dup	p.Ala17dup	inframe_insertion	1/21	1	NM_001009999.3

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151712 Hom.: 0 Cov.: 32

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

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

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:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Invitae	Mar 30, 2023	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. This variant has not been reported in the literature in individuals affected with KDM1A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This 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. -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	KDM1A: BP3 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765476443; hg19: chr1-23346116;