NM_000898.5:c.1022T>C

Variant names:

• chrX-43781451-A-G
• rs754706218
• NM_000898.5:c.1022T>C

Variant summary

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

The NM_000898.5(MAOB):​c.1022T>C​(p.Met341Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000189 in 1,059,389 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: 0.0000019 (0 hom. 1 hem.)
• Consequence: MAOB NM_000898.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.38
• 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.1022T>C	p.Met341Thr	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.1022T>C	p.Met341Thr	missense	Exon 9 of 15	ENSP00000367309.4	P27338-1
	MAOB	ENST00000890313.1		c.1127T>C	p.Met376Thr	missense	Exon 10 of 16	ENSP00000560372.1
	MAOB	ENST00000890309.1		c.1022T>C	p.Met341Thr	missense	Exon 9 of 15	ENSP00000560368.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000621 AC: 1 AN: 160929 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000134

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000189 AC: 2 AN: 1059389 Hom.: 0 Cov.: 22 AF XY: 0.00000301 AC XY: 1 AN XY: 331849

African (AFR) AF: 0.00 AC: 0 AN: 25242

American (AMR) AF: 0.00 AC: 0 AN: 32612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18645

East Asian (EAS) AF: 0.00 AC: 0 AN: 29209

South Asian (SAS) AF: 0.00 AC: 0 AN: 49179

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40031

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4013

European-Non Finnish (NFE) AF: 0.00000245 AC: 2 AN: 815869

Other (OTH) AF: 0.00 AC: 0 AN: 44589

GnomAD4 genome Cov.: 23

ExAC AF: 0.00000824 AC: 1

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	0.33
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Pathogenic	0.92	D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	0.10	D
MutationAssessor	Benign	1.7	L
PhyloP100		6.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.59
Sift	Benign	0.097	T
Sift4G	Uncertain	0.011	D
Polyphen		0.024	B
Vest4		0.49
MutPred		0.68		Loss of sheet (P = 0.0126)
MVP		0.93
MPC		0.57
ClinPred		0.48	T
GERP RS		4.3
Varity_R		0.77
gMVP		0.88
Mutation Taster		=40/60	disease causing

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: rs754706218; hg19: chrX-43640698;