1-23019631-C-G

Variant names:

• chr1-23019631-C-G
• rs755576939
• NM_001009999.3:c.35C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001009999.3(KDM1A):​c.35C>G​(p.Ala12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000079 in 1,265,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A12V) 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: 1.82

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2799756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM1A	NM_001009999.3	c.35C>G	p.Ala12Gly	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.35C>G	p.Ala12Gly	missense_variant	Exon 1 of 21	1	NM_001009999.3	ENSP00000383042.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.90e-7 AC: 1 AN: 1265400 Hom.: 0 Cov.: 31 AF XY: 0.00000161 AC XY: 1 AN XY: 622366

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: 9.75e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000965 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.65	T;T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.15	.;N;N
REVEL	Benign	0.090
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.38	.;T;T
Polyphen		0.82, 0.89	.;P;P
Vest4		0.33, 0.34
MutPred		0.45		Gain of MoRF binding (P = 0.1049);Gain of MoRF binding (P = 0.1049);Gain of MoRF binding (P = 0.1049);
MVP		0.38
MPC		1.1
ClinPred		0.74	D
GERP RS		4.3
Varity_R		0.32
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs755576939; hg19: chr1-23346124;