X-47565010-C-A

Variant names:

• chrX-47565010-C-A
• rs779648831
• NM_001654.5:c.329C>A

Variant summary

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

The NM_001654.5(ARAF):​c.329C>A​(p.Ala110Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ARAF NM_001654.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

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.329C>A	p.Ala110Glu	missense_variant	Exon 5 of 16	ENST00000377045.9	NP_001645.1
ARAF	NM_001256196.2	c.329C>A	p.Ala110Glu	missense_variant	Exon 5 of 16		NP_001243125.1
ARAF	NM_001256197.2	c.329C>A	p.Ala110Glu	missense_variant	Exon 5 of 6		NP_001243126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAF	ENST00000377045.9	c.329C>A	p.Ala110Glu	missense_variant	Exon 5 of 16	1	NM_001654.5	ENSP00000366244.4
ARAF	ENST00000377039.2	c.329C>A	p.Ala110Glu	missense_variant	Exon 5 of 6	2		ENSP00000366238.1
ARAF	ENST00000489496.1	n.249C>A		non_coding_transcript_exon_variant	Exon 4 of 4	5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	D;D;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Pathogenic	0.76	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.5	.;M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.51
MutPred		0.67		Gain of solvent accessibility (P = 0.1456);Gain of solvent accessibility (P = 0.1456);Gain of solvent accessibility (P = 0.1456);
MVP		0.97
MPC		2.4
ClinPred		1.0	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.70
gMVP		0.98

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: rs779648831; hg19: chrX-47424409;