NM_000898.5:c.1410+8A>G

Variant names:

• chrX-43768646-T-C
• rs148113949
• NM_000898.5:c.1410+8A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 gene

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.1410+8A>G		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.1410+8A>G		splice_region intron	N/A	ENSP00000367309.4	P27338-1
	MAOB	ENST00000890313.1		c.1515+8A>G		splice_region intron	N/A	ENSP00000560372.1
	MAOB	ENST00000890309.1		c.1428+8A>G		splice_region intron	N/A	ENSP00000560368.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 1614 AN: 111807 Hom.: 29 Cov.: 22

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

GnomAD2 exomes AF: 0.00436 AC: 794 AN: 182181 AF XY: 0.00322

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 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

African (AFR) AF: 0.0492 AC: 1283 AN: 26079

American (AMR) AF: 0.00319 AC: 112 AN: 35139

Ashkenazi Jewish (ASJ) AF: 0.0000520 AC: 1 AN: 19232

East Asian (EAS) AF: 0.00 AC: 0 AN: 30069

South Asian (SAS) AF: 0.000112 AC: 6 AN: 53630

European-Finnish (FIN) AF: 0.0000742 AC: 3 AN: 40441

Middle Eastern (MID) AF: 0.00269 AC: 11 AN: 4088

European-Non Finnish (NFE) AF: 0.000210 AC: 174 AN: 827286

Other (OTH) AF: 0.00367 AC: 167 AN: 45545

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

African (AFR) AF: 0.0498 AC: 1532 AN: 30751

American (AMR) AF: 0.00446 AC: 47 AN: 10531

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3544

South Asian (SAS) AF: 0.00 AC: 0 AN: 2681

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000263 AC: 14 AN: 53187

Other (OTH) AF: 0.0118 AC: 18 AN: 1530

Alfa AF: 0.0126 Hom.: 45

Bravo AF: 0.0172

EpiCase AF: 0.000110

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.68
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00040
dbscSNV1_RF	Benign	0.036
Splicevardb		1.0
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

Other links and lift over

dbSNP: rs148113949; hg19: chrX-43627893;