X-43795848-C-T

Variant names:

• chrX-43795848-C-T
• rs980435225
• NM_000898.5:c.659G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_000898.5(MAOB):​c.659G>A​(p.Arg220Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,208,016 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000010 (0 hom. 1 hem.)
• Consequence: MAOB NM_000898.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.42347473).

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.659G>A	p.Arg220Gln	missense	Exon 7 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.659G>A	p.Arg220Gln	missense	Exon 7 of 15	ENSP00000367309.4	P27338-1
	MAOB	ENST00000890313.1		c.659G>A	p.Arg220Gln	missense	Exon 7 of 16	ENSP00000560372.1
	MAOB	ENST00000890309.1		c.659G>A	p.Arg220Gln	missense	Exon 7 of 15	ENSP00000560368.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111547 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000950

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000164 AC: 3 AN: 182600 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000100 AC: 11 AN: 1096469 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 1 AN XY: 361883

African (AFR) AF: 0.00 AC: 0 AN: 26364

American (AMR) AF: 0.0000853 AC: 3 AN: 35151

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19337

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40517

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00000833 AC: 7 AN: 840729

Other (OTH) AF: 0.00 AC: 0 AN: 46029

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111547 Hom.: 0 Cov.: 22 AF XY: 0.0000296 AC XY: 1 AN XY: 33727

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000326 AC: 1 AN: 30662

American (AMR) AF: 0.0000950 AC: 1 AN: 10523

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3541

South Asian (SAS) AF: 0.00 AC: 0 AN: 2608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53104

Other (OTH) AF: 0.00 AC: 0 AN: 1490

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

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	0.088
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.5
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.34
Sift	Benign	0.33	T
Sift4G	Benign	0.20	T
Polyphen		0.35	B
Vest4		0.35
MutPred		0.55		Loss of MoRF binding (P = 0.0959)
MVP		0.89
MPC		0.59
ClinPred		0.20	T
GERP RS		4.4
Varity_R		0.17
gMVP		0.46
Mutation Taster		=75/25	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: rs980435225; hg19: chrX-43655095; COSMIC: COSV100955858; COSMIC: COSV100955858;