NM_032511.4:c.892C>G

Variant names:

• chr6-99291752-G-C
• rs193921041
• NM_032511.4:c.892C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032511.4(FAXC):​c.892C>G​(p.Gln298Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAXC NM_032511.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.59
• Publications: 1 publications found

Genes affected

FAXC (HGNC:20742): (failed axon connections homolog, metaxin like GST domain containing) Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032511.4. 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
	FAXC	NM_032511.4	MANE Select	c.892C>G	p.Gln298Glu	missense	Exon 5 of 6	NP_115900.1	Q5TGI0-1
	FAXC	NM_001346531.2		c.733C>G	p.Gln245Glu	missense	Exon 6 of 7	NP_001333460.1
	FAXC	NM_001346532.1		c.733C>G	p.Gln245Glu	missense	Exon 6 of 7	NP_001333461.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAXC	ENST00000389677.6	TSL:1 MANE Select	c.892C>G	p.Gln298Glu	missense	Exon 5 of 6	ENSP00000374328.4	Q5TGI0-1
	FAXC	ENST00000538471.1	TSL:1	c.52C>G	p.Gln18Glu	missense	Exon 2 of 3	ENSP00000445267.1	Q5TGI0-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0059	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		9.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Benign	0.27	T
Sift4G	Benign	0.91	T
Polyphen		0.42	B
Vest4		0.83
MutPred		0.71		Gain of relative solvent accessibility (P = 0.1259)
MVP		0.64
MPC		0.43
ClinPred		0.66	D
GERP RS		5.9
Varity_R		0.31
gMVP		0.88
Mutation Taster		=77/23	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: rs193921041; hg19: chr6-99739628; COSMIC: COSV67602189;