rs193921041

chr6-99291752-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAXC	NM_032511.4	c.892C>G	p.Gln298Glu	missense_variant	5/6	ENST00000389677.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAXC	ENST00000389677.6	c.892C>G	p.Gln298Glu	missense_variant	5/6	1	NM_032511.4	P1
FAXC	ENST00000538471.1	c.52C>G	p.Gln18Glu	missense_variant	2/3	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.0059	T
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.20
Sift	Benign	0.27	T;T
Sift4G	Benign	0.91	T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs193921041; hg19: chr6-99739628; COSMIC: COSV67602189;