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1-171334426-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002022.3(FMO4):c.843C>T(p.Phe281=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,571,938 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 67 hom. )

Consequence

FMO4
NM_002022.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.42
Variant links:
Genes affected
FMO4 (HGNC:3772): (flavin containing dimethylaniline monoxygenase 4) Metabolic N-oxidation of diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man. This results in a small subpopulation with reduced TMA N-oxidation capacity and causes fish odor syndrome (Trimethylaminuria). Three forms of the enzyme are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in drugs, pesticides, and xenobiotics. [provided by RefSeq, Jan 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-171334426-C-T is Benign according to our data. Variant chr1-171334426-C-T is described in ClinVar as [Benign]. Clinvar id is 708303.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.42 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FMO4NM_002022.3 linkuse as main transcriptc.843C>T p.Phe281= synonymous_variant 8/10 ENST00000367749.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FMO4ENST00000367749.4 linkuse as main transcriptc.843C>T p.Phe281= synonymous_variant 8/101 NM_002022.3 P1
FMO4ENST00000475780.5 linkuse as main transcriptn.652-2930C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00224
AC:
341
AN:
152150
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0580
Gnomad SAS
AF:
0.00290
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00535
AC:
1165
AN:
217804
Hom.:
40
AF XY:
0.00500
AC XY:
590
AN XY:
118044
show subpopulations
Gnomad AFR exome
AF:
0.000326
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0652
Gnomad SAS exome
AF:
0.00236
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000126
Gnomad OTH exome
AF:
0.00137
GnomAD4 exome
AF:
0.00170
AC:
2413
AN:
1419670
Hom.:
67
Cov.:
31
AF XY:
0.00171
AC XY:
1200
AN XY:
703586
show subpopulations
Gnomad4 AFR exome
AF:
0.0000964
Gnomad4 AMR exome
AF:
0.0000577
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0514
Gnomad4 SAS exome
AF:
0.00242
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000457
Gnomad4 OTH exome
AF:
0.00259
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00223
AC:
340
AN:
152268
Hom.:
7
Cov.:
32
AF XY:
0.00258
AC XY:
192
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0579
Gnomad4 SAS
AF:
0.00290
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000796
Hom.:
5
Bravo
AF:
0.00301
Asia WGS
AF:
0.0130
AC:
45
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
Cadd
Benign
0.056
Dann
Benign
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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.

Other links and lift over

dbSNP: rs3737926; hg19: chr1-171303565; COSMIC: COSV63001704; COSMIC: COSV63001704; API