NM_001009999.3:c.577+629A>C

Variant names:

• chr1-23045115-A-C
• rs587168
• NM_001009999.3:c.577+629A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001009999.3(KDM1A):​c.577+629A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,112 control chromosomes in the GnomAD database, including 44,814 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44814 hom., cov: 32)
• Consequence: KDM1A NM_001009999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 8 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000240553 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM1A	NM_001009999.3	c.577+629A>C		intron_variant	Intron 3 of 20	ENST00000400181.9	NP_001009999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM1A	ENST00000400181.9	c.577+629A>C		intron_variant	Intron 3 of 20	1	NM_001009999.3	ENSP00000383042.5

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115837 AN: 151994 Hom.: 44805 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.762 AC: 115884 AN: 152112 Hom.: 44814 Cov.: 32 AF XY: 0.760 AC XY: 56492 AN XY: 74348

African (AFR) AF: 0.664 AC: 27554 AN: 41470

American (AMR) AF: 0.646 AC: 9863 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2790 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4173 AN: 5180

South Asian (SAS) AF: 0.590 AC: 2846 AN: 4824

European-Finnish (FIN) AF: 0.884 AC: 9358 AN: 10580

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56710 AN: 68002

Other (OTH) AF: 0.754 AC: 1595 AN: 2114

Alfa AF: 0.806 Hom.: 25197

Bravo AF: 0.741

Asia WGS AF: 0.671 AC: 2335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	13
DANN	Benign	0.53
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs587168; hg19: chr1-23371608;