chr1-171283148-A-C

Variant names:

• chr1-171283148-A-C
• rs1126692
• NM_001282693.2:c.1188A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001282693.2(FMO1):​c.1188A>C​(p.Val396Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V396V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: FMO1 NM_001282693.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 21 publications found

Genes affected

FMO1 (HGNC:3769): (flavin containing dimethylaniline monoxygenase 1) Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-2.87 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282693.2. 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
	FMO1	NM_001282693.2	MANE Select	c.1188A>C	p.Val396Val	synonymous	Exon 8 of 9	NP_001269622.1	Q01740-1
	FMO1	NM_001282692.1		c.1200A>C	p.Val400Val	synonymous	Exon 7 of 8	NP_001269621.1	Q01740
	FMO1	NM_002021.3		c.1188A>C	p.Val396Val	synonymous	Exon 8 of 9	NP_002012.1	Q01740-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO1	ENST00000617670.6	TSL:1 MANE Select	c.1188A>C	p.Val396Val	synonymous	Exon 8 of 9	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000354841.4	TSL:1	c.1188A>C	p.Val396Val	synonymous	Exon 7 of 8	ENSP00000346901.4	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.1188A>C	p.Val396Val	synonymous	Exon 8 of 9	ENSP00000356724.3	Q01740-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.57
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1126692; hg19: chr1-171252287;