X-43793557-T-C

Variant names:

• chrX-43793557-T-C
• rs1432887350
• NM_000898.5:c.790A>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_000898.5(MAOB):​c.790A>G​(p.Ile264Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,088,076 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
• Consequence: MAOB NM_000898.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0880

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2573589).
• BP6: Variant X-43793557-T-C is Benign according to our data. Variant chrX-43793557-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3869951.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOB	NM_000898.5	c.790A>G	p.Ile264Val	missense_variant	Exon 8 of 15	ENST00000378069.5	NP_000889.3
MAOB	XM_017029524.3	c.742A>G	p.Ile248Val	missense_variant	Exon 8 of 15		XP_016885013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOB	ENST00000378069.5	c.790A>G	p.Ile264Val	missense_variant	Exon 8 of 15	1	NM_000898.5	ENSP00000367309.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000577 AC: 1 AN: 173287 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 59087

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000126

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1088076 Hom.: 0 Cov.: 27 AF XY: 0.00000564 AC XY: 2 AN XY: 354652

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.0000219

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 09, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.017
DANN	Benign	0.60
DEOGEN2	Uncertain	0.60	D
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.67	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.27
Sift	Benign	0.43	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.59		Loss of catalytic residue at P266 (P = 0.0561);
MVP		0.51
MPC		0.39
ClinPred		0.024	T
GERP RS		-4.4
Varity_R		0.086
gMVP		0.46

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: rs1432887350; hg19: chrX-43652804;