1-147187025-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001461.4(FMO5):c.1477G>A(p.Asp493Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00077 in 1,614,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D493H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00077 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 0 hom. )

Consequence

FMO5
NM_001461.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Publications

6 publications found

Variant links:

Genes affected

FMO5 (HGNC:3773): (flavin containing dimethylaniline monoxygenase 5) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

FMO5 links:

CHD1L (HGNC:1916): (chromodomain helicase DNA binding protein 1 like) This gene encodes a DNA helicase protein involved in DNA repair. The protein converts ATP to add poly(ADP-ribose) as it regulates chromatin relaxation following DNA damage. Overexpression of this gene has been linked to several types of cancers. [provided by RefSeq, Feb 2017]

CHD1L Gene-Disease associations (from GenCC):

congenital anomaly of kidney and urinary tract
Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

CHD1L links:

ENSG00000237188 (HGNC:):

ENSG00000237188 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015501469).

BS2

High AC in GnomAd4 at 118 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001461.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FMO5	NM_001461.4	MANE Select	c.1477G>A	p.Asp493Asn	missense	Exon 9 of 9	NP_001452.2	P49326-1
FMO5	NM_001144830.3		c.*266G>A		3_prime_UTR	Exon 7 of 7	NP_001138302.1	P49326-2
CHD1L	NM_001348451.2		c.-90+12440C>T		intron	N/A	NP_001335380.1	A0A0A0MSH9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FMO5	ENST00000254090.9	TSL:1 MANE Select	c.1477G>A	p.Asp493Asn	missense	Exon 9 of 9	ENSP00000254090.4	P49326-1
FMO5	ENST00000369272.7	TSL:1	c.*266G>A		3_prime_UTR	Exon 7 of 7	ENSP00000358277.3	P49326-2
FMO5	ENST00000441068.6	TSL:1	c.1257-2395G>A		intron	N/A	ENSP00000416011.2	P49326-3

Frequencies

GnomAD3 genomes

AF:

0.000775

AC:

118

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000851

AC:

214

AN:

251396

AF XY:

0.000927

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00813

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000932

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000770

AC:

1125

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000800

AC XY:

582

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000492

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00769

AC:

201

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000746

AC:

830

AN:

1111988

Other (OTH)

AF:

0.00103

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

130

194

259

324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000775

AC:

118

AN:

152316

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41568

American (AMR)

AF:

0.00118

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00103

AC:

AN:

68034

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.000869

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000692

AC:

EpiCase

AF:

0.00164

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.67

M_CAP

Benign

0.030

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

2.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

REVEL

Benign

0.089

Sift

Benign

0.078

Sift4G

Benign

0.17

Polyphen

0.017

Vest4

0.086

MVP

0.28

MPC

0.033

ClinPred

0.019

GERP RS

1.9

Varity_R

0.046

gMVP

0.38

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over