chr1-171278760-T-C

Variant names:

• chr1-171278760-T-C
• rs145849541
• NM_001282693.2:c.516T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001282693.2(FMO1):​c.516T>C​(p.His172His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,610,818 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (23 hom.)
• Consequence: FMO1 NM_001282693.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 2 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.101 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 23 AR gene

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.516T>C	p.His172His	synonymous	Exon 5 of 9	NP_001269622.1	Q01740-1
	FMO1	NM_001282692.1		c.528T>C	p.His176His	synonymous	Exon 4 of 8	NP_001269621.1	Q01740
	FMO1	NM_002021.3		c.516T>C	p.His172His	synonymous	Exon 5 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.516T>C	p.His172His	synonymous	Exon 5 of 9	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000354841.4	TSL:1	c.516T>C	p.His172His	synonymous	Exon 4 of 8	ENSP00000346901.4	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.516T>C	p.His172His	synonymous	Exon 5 of 9	ENSP00000356724.3	Q01740-1

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00185 AC: 464 AN: 250394 AF XY: 0.00259

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000987

GnomAD4 exome AF: 0.000916 AC: 1336 AN: 1458464 Hom.: 23 Cov.: 29 AF XY: 0.00142 AC XY: 1029 AN XY: 725644

African (AFR) AF: 0.0000300 AC: 1 AN: 33370

American (AMR) AF: 0.0000897 AC: 4 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39672

South Asian (SAS) AF: 0.0145 AC: 1244 AN: 85906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5754

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1109552

Other (OTH) AF: 0.000598 AC: 36 AN: 60228

GnomAD4 genome AF: 0.000400 AC: 61 AN: 152354 Hom.: 0 Cov.: 32 AF XY: 0.000617 AC XY: 46 AN XY: 74496

African (AFR) AF: 0.0000481 AC: 2 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.0000907

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.5
DANN	Benign	0.62
PhyloP100		0.10
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: rs145849541; hg19: chr1-171247899; COSMIC: COSV105906844; COSMIC: COSV105906844;