rs3027441

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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: Benign. The variant received -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.

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.1411-3T>C		splice_region intron	N/A	NP_000889.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAOB	ENST00000378069.5	TSL:1 MANE Select	c.1411-3T>C		splice_region intron	N/A	ENSP00000367309.4	P27338-1
	MAOB	ENST00000890313.1		c.1516-3T>C		splice_region intron	N/A	ENSP00000560372.1
	MAOB	ENST00000890309.1		c.1429-3T>C		splice_region intron	N/A	ENSP00000560368.1

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 6608 AN: 111541 Hom.: 360 Cov.: 23

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

GnomAD2 exomes AF: 0.0580 AC: 10242 AN: 176450 AF XY: 0.0575

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 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

African (AFR) AF: 0.151 AC: 3960 AN: 26261

American (AMR) AF: 0.0933 AC: 3237 AN: 34702

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 327 AN: 19127

East Asian (EAS) AF: 0.160 AC: 4817 AN: 30045

South Asian (SAS) AF: 0.181 AC: 9628 AN: 53200

European-Finnish (FIN) AF: 0.00342 AC: 138 AN: 40404

Middle Eastern (MID) AF: 0.0162 AC: 61 AN: 3754

European-Non Finnish (NFE) AF: 0.00246 AC: 2059 AN: 837812

Other (OTH) AF: 0.0373 AC: 1707 AN: 45795

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

African (AFR) AF: 0.145 AC: 4443 AN: 30610

American (AMR) AF: 0.0797 AC: 838 AN: 10520

Ashkenazi Jewish (ASJ) AF: 0.0215 AC: 57 AN: 2653

East Asian (EAS) AF: 0.148 AC: 521 AN: 3512

South Asian (SAS) AF: 0.179 AC: 468 AN: 2615

European-Finnish (FIN) AF: 0.00245 AC: 15 AN: 6133

Middle Eastern (MID) AF: 0.00463 AC: 1 AN: 216

European-Non Finnish (NFE) AF: 0.00350 AC: 186 AN: 53133

Other (OTH) AF: 0.0652 AC: 99 AN: 1519

Alfa AF: 0.0326 Hom.: 227

Bravo AF: 0.0690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		0.45
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3027441; hg19: chrX-43626868; COSMIC: COSV65204567;