Genetic Variant FAXDC2:p.Arg133His (chr5-154823561-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032385.5(FAXDC2):c.398G>A(p.Arg133His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 1,613,694 control chromosomes in the GnomAD database, including 5,679 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.062 ( 406 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5273 hom. )

Consequence

FAXDC2
NM_032385.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020177662).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAXDC2	NM_032385.5 link	c.398G>A	p.Arg133His	missense_variant	Exon 6 of 9	ENST00000326080.10	NP_115761.2	Q96IV6-1
FAXDC2	XM_006714753.3 link	c.398G>A	p.Arg133His	missense_variant	Exon 7 of 10		XP_006714816.1	Q96IV6-1
FAXDC2	XM_047416652.1 link	c.-23G>A		5_prime_UTR_variant	Exon 3 of 6		XP_047272608.1
FAXDC2	XM_047416654.1 link	c.-23G>A		5_prime_UTR_variant	Exon 2 of 5		XP_047272610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAXDC2	ENST00000326080.10 link	c.398G>A	p.Arg133His	missense_variant	Exon 6 of 9	1	NM_032385.5	ENSP00000320604.5		Q96IV6-1

Frequencies

GnomAD3 genomes

AF:

0.0625

AC:

9508

AN:

152064

Hom.:

407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0540

Gnomad ASJ

AF:

0.0730

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.0619

Gnomad FIN

AF:

0.0963

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0917

Gnomad OTH

AF:

0.0612

GnomAD3 exomes

AF:

0.0683

AC:

17043

AN:

249484

Hom.:

732

AF XY:

0.0702

AC XY:

9507

AN XY:

135348

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.0348

Gnomad ASJ exome

AF:

0.0721

Gnomad EAS exome

AF:

0.00612

Gnomad SAS exome

AF:

0.0658

Gnomad FIN exome

AF:

0.0991

Gnomad NFE exome

AF:

0.0898

Gnomad OTH exome

AF:

0.0781

GnomAD4 exome

AF:

0.0819

AC:

119689

AN:

1461512

Hom.:

5273

Cov.:

AF XY:

0.0819

AC XY:

59550

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.0133

Gnomad4 AMR exome

AF:

0.0354

Gnomad4 ASJ exome

AF:

0.0691

Gnomad4 EAS exome

AF:

0.00302

Gnomad4 SAS exome

AF:

0.0665

Gnomad4 FIN exome

AF:

0.0988

Gnomad4 NFE exome

AF:

0.0897

Gnomad4 OTH exome

AF:

0.0749

GnomAD4 genome

AF:

0.0624

AC:

9499

AN:

152182

Hom.:

406

Cov.:

AF XY:

0.0624

AC XY:

4641

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0151

Gnomad4 AMR

AF:

0.0539

Gnomad4 ASJ

AF:

0.0730

Gnomad4 EAS

AF:

0.00560

Gnomad4 SAS

AF:

0.0609

Gnomad4 FIN

AF:

0.0963

Gnomad4 NFE

AF:

0.0916

Gnomad4 OTH

AF:

0.0601

Alfa

AF:

0.0826

Hom.:

1216

Bravo

AF:

0.0552

TwinsUK

AF:

0.0909

AC:

337

ALSPAC

AF:

0.0838

AC:

323

ESP6500AA

AF:

0.0140

AC:

ESP6500EA

AF:

0.0922

AC:

764

ExAC

AF:

0.0675

AC:

8160

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

EpiCase

AF:

0.0907

EpiControl

AF:

0.0890

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.024

T;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.82

T;T;T

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.;.

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.096

Sift

Benign

0.54

T;T;T

Sift4G

Benign

0.55

T;T;.

Polyphen

0.010

B;.;.

Vest4

0.019

MPC

0.19

ClinPred

0.0044

GERP RS

-0.74

Varity_R

0.022

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over