1-23019621-GCC-AGT

Variant names:

• chr1-23019621-GCC-AGT
• NM_001009999.3:c.25_27delGCCinsAGT
• KDM1A p.Ala9Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001009999.3(KDM1A):​c.25_27delGCCinsAGT​(p.Ala9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM1A NM_001009999.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1A	NM_001009999.3	MANE Select	c.25_27delGCCinsAGT	p.Ala9Ser	missense	N/A	NP_001009999.1	O60341-2
	KDM1A	NM_001410762.1		c.25_27delGCCinsAGT	p.Ala9Ser	missense	N/A	NP_001397691.1	A0A8I5KXU4
	KDM1A	NM_001363654.2		c.25_27delGCCinsAGT	p.Ala9Ser	missense	N/A	NP_001350583.1	R4GMQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1A	ENST00000400181.9	TSL:1 MANE Select	c.25_27delGCCinsAGT	p.Ala9Ser	missense	N/A	ENSP00000383042.5	O60341-2
	KDM1A	ENST00000356634.7	TSL:1	c.25_27delGCCinsAGT	p.Ala9Ser	missense	N/A	ENSP00000349049.3	O60341-1
	KDM1A	ENST00000874661.1		c.25_27delGCCinsAGT	p.Ala9Ser	missense	N/A	ENSP00000544720.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

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.

Other links and lift over

hg19: chr1-23346114;