1-171207773-T-G

Variant names:

• chr1-171207773-T-G
• rs2020865
• NM_001460.5:c.1239T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001460.5(FMO2):​c.1239T>G​(p.Asn413Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 1,603,018 control chromosomes in the GnomAD database, including 5,042 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1858 hom., cov: 32)
  • Exomes 𝑓: 0.051 (3184 hom.)
• Consequence: FMO2 NM_001460.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 20 publications found

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]

ENSG00000225243 (HGNC:):

FMO1-AS1 (HGNC:40240):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039462745).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO2	NM_001460.5	MANE Select	c.1239T>G	p.Asn413Lys	missense	Exon 8 of 9	NP_001451.2	Q99518
	FMO2	NM_001365900.2		c.1044T>G	p.Asn348Lys	missense	Exon 7 of 8	NP_001352829.1
	FMO2	NM_001301347.2		c.579T>G	p.Asn193Lys	missense	Exon 6 of 7	NP_001288276.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO2	ENST00000209929.10	TSL:1 MANE Select	c.1239T>G	p.Asn413Lys	missense	Exon 8 of 9	ENSP00000209929.8	Q99518
	FMO2	ENST00000895514.1		c.1239T>G	p.Asn413Lys	missense	Exon 8 of 9	ENSP00000565573.1
	FMO2	ENST00000895513.1		c.1236T>G	p.Asn412Lys	missense	Exon 8 of 9	ENSP00000565572.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17206 AN: 151982 Hom.: 1853 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0943

GnomAD2 exomes AF: 0.0582 AC: 14510 AN: 249250 AF XY: 0.0548

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.0368

Gnomad ASJ exome AF: 0.0935

Gnomad EAS exome AF: 0.000546

Gnomad FIN exome AF: 0.0219

Gnomad NFE exome AF: 0.0461

Gnomad OTH exome AF: 0.0523

GnomAD4 exome AF: 0.0508 AC: 73654 AN: 1450918 Hom.: 3184 Cov.: 27 AF XY: 0.0501 AC XY: 36171 AN XY: 722330

African (AFR) AF: 0.295 AC: 9667 AN: 32780

American (AMR) AF: 0.0403 AC: 1791 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.0910 AC: 2362 AN: 25970

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39610

South Asian (SAS) AF: 0.0530 AC: 4544 AN: 85670

European-Finnish (FIN) AF: 0.0210 AC: 1124 AN: 53404

Middle Eastern (MID) AF: 0.0777 AC: 445 AN: 5730

European-Non Finnish (NFE) AF: 0.0453 AC: 50032 AN: 1103374

Other (OTH) AF: 0.0614 AC: 3681 AN: 59944

GnomAD4 genome AF: 0.113 AC: 17233 AN: 152100 Hom.: 1858 Cov.: 32 AF XY: 0.109 AC XY: 8120 AN XY: 74368

African (AFR) AF: 0.292 AC: 12104 AN: 41450

American (AMR) AF: 0.0606 AC: 927 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 341 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4820

European-Finnish (FIN) AF: 0.0220 AC: 233 AN: 10586

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0463 AC: 3148 AN: 67988

Other (OTH) AF: 0.0933 AC: 197 AN: 2112

Alfa AF: 0.0662 Hom.: 3045

Bravo AF: 0.125

TwinsUK AF: 0.0440 AC: 163

ALSPAC AF: 0.0413 AC: 159

ESP6500AA AF: 0.279 AC: 1230

ESP6500EA AF: 0.0491 AC: 422

ExAC AF: 0.0631 AC: 7658

EpiCase AF: 0.0541

EpiControl AF: 0.0567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.3
DANN	Benign	0.73
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.060
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.94	N
REVEL	Benign	0.087
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.051
MutPred		0.47		Gain of sheet (P = 0.0085)
ClinPred		0.0021	T
GERP RS		-1.1
gMVP		0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs2020865; hg19: chr1-171176912; COSMIC: COSV52947653; COSMIC: COSV52947653;