chrX-43797156-G-T

Variant names:

• chrX-43797156-G-T
• rs781450685
• NM_000898.5:c.587C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000898.5(MAOB):​c.587C>A​(p.Thr196Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,094,977 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T196R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: MAOB NM_000898.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36706161).

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.587C>A	p.Thr196Lys	missense	Exon 6 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.587C>A	p.Thr196Lys	missense	Exon 6 of 15	ENSP00000367309.4	P27338-1
	MAOB	ENST00000890313.1		c.587C>A	p.Thr196Lys	missense	Exon 6 of 16	ENSP00000560372.1
	MAOB	ENST00000890309.1		c.587C>A	p.Thr196Lys	missense	Exon 6 of 15	ENSP00000560368.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1094977 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 360601

African (AFR) AF: 0.00 AC: 0 AN: 26342

American (AMR) AF: 0.00 AC: 0 AN: 34986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19348

East Asian (EAS) AF: 0.00 AC: 0 AN: 30133

South Asian (SAS) AF: 0.00 AC: 0 AN: 53401

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840148

Other (OTH) AF: 0.00 AC: 0 AN: 45985

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.58
DEOGEN2	Uncertain	0.76	D
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.28
Sift	Benign	0.39	T
Sift4G	Benign	0.93	T
Polyphen		0.012	B
Vest4		0.30
MutPred		0.77		Gain of methylation at T196 (P = 0.0046)
MVP		0.78
MPC		0.57
ClinPred		0.31	T
GERP RS		3.6
Varity_R		0.46
gMVP		0.66
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs781450685; hg19: chrX-43656403;