chrX-43781509-C-T

Variant names:

• chrX-43781509-C-T
• rs1486086634
• NM_000898.5:c.964G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000898.5(MAOB):​c.964G>A​(p.Ala322Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,326 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
• Consequence: MAOB NM_000898.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55
• Publications: 0 publications found

Genes affected

MAOB (HGNC:6834): (monoamine oxidase B) The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is a enzyme located in the mitochondrial outer membrane. It catalyzes the oxidative deamination of biogenic and xenobiotic amines and plays an important role in the metabolism of neuroactive and vasoactive amines in the central nervous sysytem and peripheral tissues. This protein preferentially degrades benzylamine and phenylethylamine. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000898.5. 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
	MAOB	NM_000898.5	MANE Select	c.964G>A	p.Ala322Thr	missense	Exon 9 of 15	NP_000889.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAOB	ENST00000378069.5	TSL:1 MANE Select	c.964G>A	p.Ala322Thr	missense	Exon 9 of 15	ENSP00000367309.4	P27338-1
	MAOB	ENST00000890313.1		c.1069G>A	p.Ala357Thr	missense	Exon 10 of 16	ENSP00000560372.1
	MAOB	ENST00000890309.1		c.964G>A	p.Ala322Thr	missense	Exon 9 of 15	ENSP00000560368.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.23e-7 AC: 1 AN: 1083326 Hom.: 0 Cov.: 26 AF XY: 0.00000286 AC XY: 1 AN XY: 349908

African (AFR) AF: 0.00 AC: 0 AN: 25960

American (AMR) AF: 0.00 AC: 0 AN: 34415

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19181

East Asian (EAS) AF: 0.0000335 AC: 1 AN: 29820

South Asian (SAS) AF: 0.00 AC: 0 AN: 52248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4086

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831744

Other (OTH) AF: 0.00 AC: 0 AN: 45546

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.69	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	1.9	L
PhyloP100		3.5
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.63
Sift	Benign	0.054	T
Sift4G	Benign	0.10	T
Polyphen		0.36	B
Vest4		0.33
MutPred		0.52		Gain of phosphorylation at A322 (P = 0.033)
MVP		0.93
MPC		0.47
ClinPred		0.87	D
GERP RS		5.5
Varity_R		0.63
gMVP		0.84
Mutation Taster		=51/49	polymorphism

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: rs1486086634; hg19: chrX-43640756;