X-47563013-C-G

Variant names:

• chrX-47563013-C-G
• NM_001654.5:c.46C>G

Variant summary

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

The NM_001654.5(ARAF):​c.46C>G​(p.Arg16Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000922 in 1,084,475 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
• Consequence: ARAF NM_001654.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87

Genes affected

ARAF (HGNC:646): (A-Raf proto-oncogene, serine/threonine kinase) Enables protein serine/threonine kinase activity. Involved in negative regulation of apoptotic process; regulation of TOR signaling; and regulation of cellular protein metabolic process. Predicted to be active in cytosol and mitochondrion. Biomarker of high grade glioma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAF	NM_001654.5	c.46C>G	p.Arg16Gly	missense_variant	Exon 2 of 16	ENST00000377045.9	NP_001645.1
ARAF	NM_001256196.2	c.46C>G	p.Arg16Gly	missense_variant	Exon 2 of 16		NP_001243125.1
ARAF	NM_001256197.2	c.46C>G	p.Arg16Gly	missense_variant	Exon 2 of 6		NP_001243126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAF	ENST00000377045.9	c.46C>G	p.Arg16Gly	missense_variant	Exon 2 of 16	1	NM_001654.5	ENSP00000366244.4
ARAF	ENST00000377039.2	c.46C>G	p.Arg16Gly	missense_variant	Exon 2 of 6	2		ENSP00000366238.1
ARAF	ENST00000489496.1	n.-39C>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.22e-7 AC: 1 AN: 1084475 Hom.: 0 Cov.: 30 AF XY: 0.00000282 AC XY: 1 AN XY: 354309

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: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;D;.
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Pathogenic	0.91	D
MutationAssessor	Benign	1.4	.;L;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.88	.;P;.
Vest4		0.58
MutPred		0.26		Loss of MoRF binding (P = 0.0185);Loss of MoRF binding (P = 0.0185);Loss of MoRF binding (P = 0.0185);
MVP		0.95
MPC		2.0
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.30
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-47422412;