rs982751376

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-154823474-C-T
• chr5-154823474-C-G

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>A​(p.Arg162His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: FAXDC2 NM_032385.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.14623863).

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>A	p.Arg162His	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>A	p.Arg162His	missense	Exon 6 of 9	ENSP00000320604.5	Q96IV6-1
	FAXDC2	ENST00000962790.1		c.485G>A	p.Arg162His	missense	Exon 6 of 10	ENSP00000632849.1
	FAXDC2	ENST00000888402.1		c.485G>A	p.Arg162His	missense	Exon 8 of 11	ENSP00000558461.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249518 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74324

African (AFR) AF: 0.0000483 AC: 2 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.00046	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.026
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.9
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.086
Sift	Benign	0.54	T
Sift4G	Benign	0.20	T
Polyphen		0.52	P
Vest4		0.059
MutPred		0.40		Loss of MoRF binding (P = 0.075)
MVP		0.50
MPC		0.19
ClinPred		0.23	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.029
gMVP		0.31
Mutation Taster		=75/25	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; COSMIC: COSV58172608; COSMIC: COSV58172608;