Variant 1-171205432-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001460.5(FMO2):c.981T>G(p.Phe327Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

FMO2
NM_001460.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.442

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FMO2	NM_001460.5 linkuse as main transcript	c.981T>G	p.Phe327Leu	missense_variant	7/9	ENST00000209929.10
LOC124900413	XR_007066731.1 linkuse as main transcript	n.366-8494A>C		intron_variant, non_coding_transcript_variant
LOC105371611	XR_922278.4 linkuse as main transcript	n.515-37244A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FMO2	ENST00000209929.10 linkuse as main transcript	c.981T>G	p.Phe327Leu	missense_variant	7/9	1	NM_001460.5	P1
	ENST00000445290.1 linkuse as main transcript	n.139-5917A>C		intron_variant, non_coding_transcript_variant		2
	ENST00000669750.1 linkuse as main transcript	n.449-37244A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727114

show subpopulations

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:

0.0000216

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.981T>G (p.F327L) alteration is located in exon 7 (coding exon 6) of the FMO2 gene. This alteration results from a T to G substitution at nucleotide position 981, causing the phenylalanine (F) at amino acid position 327 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.69

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.1

REVEL

Uncertain

0.37

Sift

Benign

0.049

Sift4G

Benign

0.068

Vest4

0.34

MutPred

0.62

Loss of sheet (P = 0.1158);

MVP

0.83

ClinPred

0.99

GERP RS

2.2

gMVP

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over