X-43775281-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000898.5(MAOB):c.1138-9A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0005 in 1,199,342 control chromosomes in the GnomAD database, including 1 homozygotes. There are 187 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., 11 hem., cov: 22)
  • Exomes 𝑓: 0.00052 (1 hom. 176 hem.)
• Consequence: MAOB NM_000898.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004538
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0790

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-43775281-T-C is Benign according to our data. Variant chrX-43775281-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 713666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAOB	NM_000898.5	c.1138-9A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000378069.5
MAOB	XM_017029524.3	c.1090-9A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAOB	ENST00000378069.5	c.1138-9A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000898.5	P1

Frequencies

GnomAD3 genomes AF: 0.000350 AC: 39 AN: 111301 Hom.: 0 Cov.: 22 AF XY: 0.000328 AC XY: 11 AN XY: 33517

Gnomad AFR AF: 0.000131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000189

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000284 AC: 46 AN: 161942 Hom.: 0 AF XY: 0.000307 AC XY: 15 AN XY: 48932

Gnomad AFR exome AF: 0.000170

Gnomad AMR exome AF: 0.000609

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000323

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000349

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000516 AC: 561 AN: 1087988 Hom.: 1 Cov.: 32 AF XY: 0.000496 AC XY: 176 AN XY: 354742

Gnomad4 AFR exome AF: 0.000115

Gnomad4 AMR exome AF: 0.000531

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00994

Gnomad4 SAS exome AF: 0.0000387

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000278

Gnomad4 OTH exome AF: 0.000197

GnomAD4 genome AF: 0.000350 AC: 39 AN: 111354 Hom.: 0 Cov.: 22 AF XY: 0.000328 AC XY: 11 AN XY: 33580

Gnomad4 AFR AF: 0.000130

Gnomad4 AMR AF: 0.00115

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00368

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000189

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000217 Hom.: 1

Bravo AF: 0.000332

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.5
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000045
dbscSNV1_RF	Benign	0.0020
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: rs180812382; hg19: chrX-43634528;