X-43781509-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOB	NM_000898.5	c.964G>A	p.Ala322Thr	missense_variant	Exon 9 of 15	ENST00000378069.5	NP_000889.3
MAOB	XM_017029524.3	c.916G>A	p.Ala306Thr	missense_variant	Exon 9 of 15		XP_016885013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOB	ENST00000378069.5	c.964G>A	p.Ala322Thr	missense_variant	Exon 9 of 15	1	NM_000898.5	ENSP00000367309.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000335

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.964G>A (p.A322T) alteration is located in exon 9 (coding exon 9) of the MAOB gene. This alteration results from a G to A substitution at nucleotide position 964, causing the alanine (A) at amino acid position 322 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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: rs1486086634; hg19: chrX-43640756;