5-154823474-C-G

Variant names:

• chr5-154823474-C-G
• rs982751376
• NM_032385.5:c.485G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032385.5(FAXDC2):​c.485G>C​(p.Arg162Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. R162H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAXDC2 NM_032385.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1881316).

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.485G>C	p.Arg162Pro	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.485G>C	p.Arg162Pro	missense	Exon 6 of 9	ENSP00000320604.5	Q96IV6-1
	FAXDC2	ENST00000962790.1		c.485G>C	p.Arg162Pro	missense	Exon 6 of 10	ENSP00000632849.1
	FAXDC2	ENST00000888402.1		c.485G>C	p.Arg162Pro	missense	Exon 8 of 11	ENSP00000558461.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	0.0040	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.00019	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.9
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.49	N
REVEL	Uncertain	0.32
Sift	Benign	0.21	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.41
MutPred		0.51		Loss of loop (P = 0.0374)
MVP		0.38
MPC		0.30
ClinPred		0.47	T
GERP RS		2.8
Varity_R		0.14
gMVP		0.66
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs982751376; hg19: chr5-154203034;