rs915595049

Variant names:

• chr1-23019643-C-G
• NM_001009999.3:c.47C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-23019643-C-G
• chr1-23019643-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009999.3(KDM1A):​c.47C>G​(p.Ala16Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000794 in 1,258,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A16V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: KDM1A NM_001009999.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1803793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM1A	NM_001009999.3	c.47C>G	p.Ala16Gly	missense_variant	Exon 1 of 21	ENST00000400181.9	NP_001009999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM1A	ENST00000400181.9	c.47C>G	p.Ala16Gly	missense_variant	Exon 1 of 21	1	NM_001009999.3	ENSP00000383042.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.94e-7 AC: 1 AN: 1258658 Hom.: 0 Cov.: 31 AF XY: 0.00000162 AC XY: 1 AN XY: 618620

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.79e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.30	.;N;N
REVEL	Benign	0.045
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.083	.;T;T
Polyphen		0.0	.;B;B
Vest4		0.27, 0.30
MutPred		0.26		Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);
MVP		0.37
MPC		1.1
ClinPred		0.52	D
GERP RS		2.3
Varity_R		0.13
gMVP		0.14

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-23346136;