Genetic Variant NM_032385.5:c.829G>A (chr5-154821276-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_032385.5(FAXDC2):c.829G>A(p.Asp277Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000378 in 1,611,562 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

FAXDC2
NM_032385.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84

Publications

2 publications found

Variant links:

Genes affected

FAXDC2 (HGNC:1334): (fatty acid hydroxylase domain containing 2) Predicted to enable C-4 methylsterol oxidase activity. Involved in positive regulation of megakaryocyte differentiation and positive regulation of protein phosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAXDC2 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

FAXDC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032385.5. 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
	FAXDC2	NM_032385.5	MANE Select	c.829G>A	p.Asp277Asn	missense	Exon 8 of 9	NP_115761.2	Q96IV6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAXDC2	ENST00000326080.10	TSL:1 MANE Select	c.829G>A	p.Asp277Asn	missense	Exon 8 of 9	ENSP00000320604.5	Q96IV6-1
FAXDC2	ENST00000962790.1		c.829G>A	p.Asp277Asn	missense	Exon 8 of 10	ENSP00000632849.1
FAXDC2	ENST00000888402.1		c.829G>A	p.Asp277Asn	missense	Exon 10 of 11	ENSP00000558461.1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000296

AC:

AN:

247034

AF XY:

0.000306

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.0000568

Gnomad FIN exome

AF:

0.000604

Gnomad NFE exome

AF:

0.000321

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000392

AC:

572

AN:

1459566

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

284

AN XY:

726082

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33258

American (AMR)

AF:

0.0000899

AC:

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.00157

AC:

AN:

26068

East Asian (EAS)

AF:

0.000102

AC:

AN:

39356

South Asian (SAS)

AF:

0.000290

AC:

AN:

86092

European-Finnish (FIN)

AF:

0.000506

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.000403

AC:

448

AN:

1110868

Other (OTH)

AF:

0.000348

AC:

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000243

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41380

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

67990

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.000417

Hom.:

Bravo

AF:

0.000185

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000330

AC:

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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.8

PhyloP100

5.8

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.34

Sift

Uncertain

0.023

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.75

MVP

0.32

MPC

0.65

ClinPred

0.84

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.52

gMVP

0.87

Mutation Taster

=51/49

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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