rs6324

Positions:

• chrX-43767568-G-A
• chrX-43767568-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000898.5(MAOB):​c.1461C>T​(p.Pro487Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,208,570 control chromosomes in the GnomAD database, including 1,005 homozygotes. There are 10,534 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.028 (102 hom., 983 hem., cov: 22)
  • Exomes 𝑓: 0.021 (903 hom. 9551 hem.)
• Consequence: MAOB NM_000898.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.506 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAOB	NM_000898.5	c.1461C>T	p.Pro487Pro	synonymous_variant	15/15	ENST00000378069.5	NP_000889.3
MAOB	XM_017029524.3	c.1413C>T	p.Pro471Pro	synonymous_variant	15/15		XP_016885013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAOB	ENST00000378069.5	c.1461C>T	p.Pro487Pro	synonymous_variant	15/15	1	NM_000898.5	ENSP00000367309.4

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 3085 AN: 111629 Hom.: 99 Cov.: 22 AF XY: 0.0290 AC XY: 981 AN XY: 33789

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.0212

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.00262

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.00333

Gnomad OTH AF: 0.0279

GnomAD3 exomes AF: 0.0500 AC: 9118 AN: 182202 Hom.: 368 AF XY: 0.0544 AC XY: 3639 AN XY: 66842

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.0903

Gnomad ASJ exome AF: 0.0167

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.00307

Gnomad NFE exome AF: 0.00316

Gnomad OTH exome AF: 0.0335

GnomAD4 exome AF: 0.0206 AC: 22599 AN: 1096885 Hom.: 903 Cov.: 29 AF XY: 0.0264 AC XY: 9551 AN XY: 362399

Gnomad4 AFR exome AF: 0.0363

Gnomad4 AMR exome AF: 0.0877

Gnomad4 ASJ exome AF: 0.0170

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.00343

Gnomad4 NFE exome AF: 0.00240

Gnomad4 OTH exome AF: 0.0303

GnomAD4 genome AF: 0.0277 AC: 3093 AN: 111685 Hom.: 102 Cov.: 22 AF XY: 0.0290 AC XY: 983 AN XY: 33855

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.0671

Gnomad4 ASJ AF: 0.0212

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.00262

Gnomad4 NFE AF: 0.00333

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0125 Hom.: 849

Bravo AF: 0.0323

EpiCase AF: 0.00421

EpiControl AF: 0.00250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.1
DANN	Benign	0.60

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: rs6324; hg19: chrX-43626815; COSMIC: COSV65204543;