1-23019623-CGCGGCGGCG-CGCG

Variant names:

• chr1-23019623-CGCGGCG-C
• rs765476443
• NM_001009999.3:c.36_41delGGCGGC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001009999.3(KDM1A):​c.36_41delGGCGGC​(p.Ala13_Ala14del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000079 in 1,266,374 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A12A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: KDM1A NM_001009999.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001009999.3

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.36_41delGGCGGC	p.Ala13_Ala14del	disruptive_inframe_deletion	Exon 1 of 21	NP_001009999.1	O60341-2
	KDM1A	NM_001410762.1		c.36_41delGGCGGC	p.Ala13_Ala14del	disruptive_inframe_deletion	Exon 1 of 20	NP_001397691.1	A0A8I5KXU4
	KDM1A	NM_001363654.2		c.36_41delGGCGGC	p.Ala13_Ala14del	disruptive_inframe_deletion	Exon 1 of 19	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.36_41delGGCGGC	p.Ala13_Ala14del	disruptive_inframe_deletion	Exon 1 of 21	ENSP00000383042.5	O60341-2
	KDM1A	ENST00000356634.7	TSL:1	c.36_41delGGCGGC	p.Ala13_Ala14del	disruptive_inframe_deletion	Exon 1 of 19	ENSP00000349049.3	O60341-1
	KDM1A	ENST00000874661.1		c.36_41delGGCGGC	p.Ala13_Ala14del	disruptive_inframe_deletion	Exon 1 of 21	ENSP00000544720.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.90e-7 AC: 1 AN: 1266374 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 623034

African (AFR) AF: 0.0000393 AC: 1 AN: 25464

American (AMR) AF: 0.00 AC: 0 AN: 17278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19726

East Asian (EAS) AF: 0.00 AC: 0 AN: 29544

South Asian (SAS) AF: 0.00 AC: 0 AN: 60458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3552

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1027242

Other (OTH) AF: 0.00 AC: 0 AN: 51838

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs765476443; hg19: chr1-23346116;