X-43802257-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000898.5(MAOB):c.391A>C(p.Ser131Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: MAOB NM_000898.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21376893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAOB	NM_000898.5	c.391A>C	p.Ser131Arg	missense_variant	5/15	ENST00000378069.5
MAOB	XM_017029524.3	c.343A>C	p.Ser115Arg	missense_variant	5/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAOB	ENST00000378069.5	c.391A>C	p.Ser131Arg	missense_variant	5/15	1	NM_000898.5	P1
MAOB	ENST00000487544.1	n.717A>C		non_coding_transcript_exon_variant	6/7	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000590 AC: 1 AN: 169455 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 55383

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000134

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000825 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2023

The c.391A>C (p.S131R) alteration is located in exon 5 (coding exon 5) of the MAOB gene. This alteration results from a A to C substitution at nucleotide position 391, causing the serine (S) at amino acid position 131 to be replaced by an arginine (R). 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	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	18
Dann	Benign	0.93
DEOGEN2	Uncertain	0.71	D
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Benign	-0.52	N
MutationTaster	Benign	0.70	D;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.31
Sift	Benign	0.52	T
Sift4G	Benign	0.58	T
Polyphen		0.0050	B
Vest4		0.14
MutPred		0.55		Gain of sheet (P = 0.0125);
MVP		0.62
MPC		0.54
ClinPred		0.12	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.47

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: rs766904222; hg19: chrX-43661504;