5-154823561-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032385.5(FAXDC2):​c.398G>C​(p.Arg133Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R133H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAXDC2 NM_032385.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11657372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAXDC2	NM_032385.5	c.398G>C	p.Arg133Pro	missense_variant	Exon 6 of 9	ENST00000326080.10	NP_115761.2
FAXDC2	XM_006714753.3	c.398G>C	p.Arg133Pro	missense_variant	Exon 7 of 10		XP_006714816.1
FAXDC2	XM_047416652.1	c.-23G>C		5_prime_UTR_variant	Exon 3 of 6		XP_047272608.1
FAXDC2	XM_047416654.1	c.-23G>C		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	c.398G>C	p.Arg133Pro	missense_variant	Exon 6 of 9	1	NM_032385.5	ENSP00000320604.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461796 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.071	T;.;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.23	T;T;.
Polyphen		0.0	B;.;.
Vest4		0.15
MutPred		0.48		Loss of catalytic residue at R133 (P = 0.0379);.;.;
MVP		0.16
MPC		0.23
ClinPred		0.10	T
GERP RS		-0.74
Varity_R		0.40
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-154203121;