rs3027441

Variant names:

• chrX-43767621-A-G
• rs3027441
• NM_000898.5:c.1411-3T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000898.5(MAOB):​c.1411-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,202,693 control chromosomes in the GnomAD database, including 1,485 homozygotes. There are 12,248 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.059 (363 hom., 1928 hem., cov: 23)
  • Exomes 𝑓: 0.024 (1122 hom. 10320 hem.)
• Consequence: MAOB NM_000898.5 splice_region, intron
• Scores: Splicing: ADA: 0.0002508
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOB	NM_000898.5	c.1411-3T>C		splice_region_variant, intron_variant	Intron 14 of 14	ENST00000378069.5	NP_000889.3
MAOB	XM_017029524.3	c.1363-3T>C		splice_region_variant, intron_variant	Intron 14 of 14		XP_016885013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOB	ENST00000378069.5	c.1411-3T>C		splice_region_variant, intron_variant	Intron 14 of 14	1	NM_000898.5	ENSP00000367309.4

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 6608 AN: 111541 Hom.: 360 Cov.: 23 AF XY: 0.0568 AC XY: 1916 AN XY: 33735

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0801

Gnomad ASJ AF: 0.0215

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00844

Gnomad NFE AF: 0.00350

Gnomad OTH AF: 0.0560

GnomAD3 exomes AF: 0.0580 AC: 10242 AN: 176450 Hom.: 472 AF XY: 0.0575 AC XY: 3564 AN XY: 62004

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.0934

Gnomad ASJ exome AF: 0.0163

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.187

Gnomad FIN exome AF: 0.00305

Gnomad NFE exome AF: 0.00326

Gnomad OTH exome AF: 0.0378

GnomAD4 exome AF: 0.0238 AC: 25934 AN: 1091100 Hom.: 1122 Cov.: 29 AF XY: 0.0289 AC XY: 10320 AN XY: 357250

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.0933

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.00342

Gnomad4 NFE exome AF: 0.00246

Gnomad4 OTH exome AF: 0.0373

GnomAD4 genome AF: 0.0594 AC: 6628 AN: 111593 Hom.: 363 Cov.: 23 AF XY: 0.0570 AC XY: 1928 AN XY: 33797

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0797

Gnomad4 ASJ AF: 0.0215

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00350

Gnomad4 OTH AF: 0.0652

Alfa AF: 0.0326 Hom.: 227

Bravo AF: 0.0690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00025
dbscSNV1_RF	Benign	0.042
SpliceAI score (max)		0.12		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: rs3027441; hg19: chrX-43626868; COSMIC: COSV65204567;