Genetic Variant FMO2:p.Ser195* (chr1-171199445-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001460.5(FMO2):c.584C>A(p.Ser195*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)

Consequence

FMO2
NM_001460.5 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.80

Publications

42 publications found

Variant links:

Genes affected

FMO2 (HGNC:3770): (flavin containing dimethylaniline monoxygenase 2) This gene encodes a flavin-containing monooxygenase family member. It is an NADPH-dependent enzyme that catalyzes the N-oxidation of some primary alkylamines through an N-hydroxylamine intermediate. However, some human populations contain an allele (FMO2*2A) with a premature stop codon, resulting in a protein that is C-terminally-truncated, has no catalytic activity, and is likely degraded rapidly. This gene is found in a cluster with other related family members on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

FMO2 links:

ENSG00000225243 (HGNC:):

ENSG00000225243 links:

ENSG00000231424 (HGNC:40240):

ENSG00000231424 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001460.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FMO2	NM_001460.5	MANE Select	c.584C>A	p.Ser195*	stop_gained	Exon 5 of 9	NP_001451.2
FMO2	NM_001365900.2		c.389C>A	p.Ser130*	stop_gained	Exon 4 of 8	NP_001352829.1
FMO2	NM_001301347.2		c.-34+2634C>A		intron	N/A	NP_001288276.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FMO2	ENST00000209929.10	TSL:1 MANE Select	c.584C>A	p.Ser195*	stop_gained	Exon 5 of 9	ENSP00000209929.8
ENSG00000225243	ENST00000422841.5	TSL:3	n.457G>T		non_coding_transcript_exon	Exon 3 of 3
ENSG00000225243	ENST00000445290.1	TSL:2	n.209G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.66

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

PhyloP100

7.8

Vest4

0.88

GERP RS

6.2

Mutation Taster

=51/149

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.25

Position offset: 43

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over