5-154823561-C-T

Variant names:

• chr5-154823561-C-T
• rs17641488
• NM_032385.5:c.398G>A

Variant summary

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

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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R133L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.062 (406 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5273 hom.)
• Consequence: FAXDC2 NM_032385.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 18 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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.

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.398G>A	p.Arg133His	missense	Exon 6 of 9	NP_115761.2	Q96IV6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAXDC2	ENST00000326080.10	TSL:1 MANE Select	c.398G>A	p.Arg133His	missense	Exon 6 of 9	ENSP00000320604.5	Q96IV6-1
	FAXDC2	ENST00000962790.1		c.398G>A	p.Arg133His	missense	Exon 6 of 10	ENSP00000632849.1
	FAXDC2	ENST00000888402.1		c.398G>A	p.Arg133His	missense	Exon 8 of 11	ENSP00000558461.1

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9508 AN: 152064 Hom.: 407 Cov.: 32

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

GnomAD2 exomes AF: 0.0683 AC: 17043 AN: 249484 AF XY: 0.0702

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 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.: 32 AF XY: 0.0819 AC XY: 59550 AN XY: 727058

African (AFR) AF: 0.0133 AC: 446 AN: 33480

American (AMR) AF: 0.0354 AC: 1582 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0691 AC: 1806 AN: 26126

East Asian (EAS) AF: 0.00302 AC: 120 AN: 39700

South Asian (SAS) AF: 0.0665 AC: 5733 AN: 86246

European-Finnish (FIN) AF: 0.0988 AC: 5275 AN: 53410

Middle Eastern (MID) AF: 0.0859 AC: 495 AN: 5764

European-Non Finnish (NFE) AF: 0.0897 AC: 99712 AN: 1111686

Other (OTH) AF: 0.0749 AC: 4520 AN: 60380

GnomAD4 genome AF: 0.0624 AC: 9499 AN: 152182 Hom.: 406 Cov.: 32 AF XY: 0.0624 AC XY: 4641 AN XY: 74406

African (AFR) AF: 0.0151 AC: 626 AN: 41536

American (AMR) AF: 0.0539 AC: 825 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0730 AC: 253 AN: 3468

East Asian (EAS) AF: 0.00560 AC: 29 AN: 5174

South Asian (SAS) AF: 0.0609 AC: 294 AN: 4824

European-Finnish (FIN) AF: 0.0963 AC: 1020 AN: 10594

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0916 AC: 6230 AN: 67976

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0775 Hom.: 1584

Bravo AF: 0.0552

TwinsUK AF: 0.0909 AC: 337

ALSPAC AF: 0.0838 AC: 323

ESP6500AA AF: 0.0140 AC: 56

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.73
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-1.1
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.096
Sift	Benign	0.54	T
Sift4G	Benign	0.55	T
Polyphen		0.010	B
Vest4		0.019
MPC		0.19
ClinPred		0.0044	T
GERP RS		-0.74
Varity_R		0.022
gMVP		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17641488; hg19: chr5-154203121; COSMIC: COSV58174208; COSMIC: COSV58174208;