X-43810702-A-T

Variant names:

• chrX-43810702-A-T
• rs12394221
• NM_000898.5:c.280-7298T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000898.5(MAOB):​c.280-7298T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 111,892 control chromosomes in the GnomAD database, including 4 homozygotes. There are 173 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 0.0053 (4 hom., 173 hem., cov: 23)
• Consequence: MAOB NM_000898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595

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=-0.91).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0053 (593/111892) while in subpopulation AFR AF= 0.0177 (543/30663). AF 95% confidence interval is 0.0165. There are 4 homozygotes in gnomad4. There are 173 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOB	NM_000898.5	c.280-7298T>A		intron_variant	Intron 3 of 14	ENST00000378069.5	NP_000889.3
MAOB	XM_017029524.3	c.232-7298T>A		intron_variant	Intron 3 of 14		XP_016885013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOB	ENST00000378069.5	c.280-7298T>A		intron_variant	Intron 3 of 14	1	NM_000898.5	ENSP00000367309.4
MAOB	ENST00000487544.1	n.606-7298T>A		intron_variant	Intron 4 of 6	5

Frequencies

GnomAD3 genomes AF: 0.00521 AC: 583 AN: 111839 Hom.: 4 Cov.: 23 AF XY: 0.00482 AC XY: 164 AN XY: 34005

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00368

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000939

Gnomad OTH AF: 0.00395

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00530 AC: 593 AN: 111892 Hom.: 4 Cov.: 23 AF XY: 0.00508 AC XY: 173 AN XY: 34068

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.00368

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000939

Gnomad4 OTH AF: 0.00391

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.41

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: rs12394221; hg19: chrX-43669949; COSMIC: COSV65206724;