X-43768646-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000898.5(MAOB):c.1410+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,193,371 control chromosomes in the GnomAD database, including 54 homozygotes. There are 907 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (29 hom., 444 hem., cov: 22)
  • Exomes 𝑓: 0.0016 (25 hom. 463 hem.)
• Consequence: MAOB NM_000898.5 splice_region, intron
• Scores: Splicing: ADA: 0.0004028
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.325

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-43768646-T-C is Benign according to our data. Variant chrX-43768646-T-C is described in ClinVar as [Benign]. Clinvar id is 791380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (1612/111862) while in subpopulation AFR AF= 0.0498 (1532/30751). AF 95% confidence interval is 0.0477. There are 29 homozygotes in gnomad4. There are 444 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 29 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAOB	NM_000898.5	c.1410+8A>G		splice_region_variant, intron_variant		ENST00000378069.5
MAOB	XM_017029524.3	c.1362+8A>G		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAOB	ENST00000378069.5	c.1410+8A>G		splice_region_variant, intron_variant		1	NM_000898.5	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 1614 AN: 111807 Hom.: 29 Cov.: 22 AF XY: 0.0130 AC XY: 441 AN XY: 33999

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00447

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000263

Gnomad OTH AF: 0.0119

GnomAD3 exomes AF: 0.00436 AC: 794 AN: 182181 Hom.: 17 AF XY: 0.00322 AC XY: 215 AN XY: 66859

Gnomad AFR exome AF: 0.0527

Gnomad AMR exome AF: 0.00282

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000106

Gnomad FIN exome AF: 0.000125

Gnomad NFE exome AF: 0.000172

Gnomad OTH exome AF: 0.00178

GnomAD4 exome AF: 0.00162 AC: 1757 AN: 1081509 Hom.: 25 Cov.: 26 AF XY: 0.00133 AC XY: 463 AN XY: 348609

Gnomad4 AFR exome AF: 0.0492

Gnomad4 AMR exome AF: 0.00319

Gnomad4 ASJ exome AF: 0.0000520

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000112

Gnomad4 FIN exome AF: 0.0000742

Gnomad4 NFE exome AF: 0.000210

Gnomad4 OTH exome AF: 0.00367

GnomAD4 genome AF: 0.0144 AC: 1612 AN: 111862 Hom.: 29 Cov.: 22 AF XY: 0.0130 AC XY: 444 AN XY: 34064

Gnomad4 AFR AF: 0.0498

Gnomad4 AMR AF: 0.00446

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000282

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000263

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0126 Hom.: 45

Bravo AF: 0.0172

EpiCase AF: 0.000110

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.8
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00040
dbscSNV1_RF	Benign	0.036
SpliceAI score (max)		0.010		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: rs148113949; hg19: chrX-43627893;