rs746126878

Variant names:

• chrX-47565132-C-A
• NM_001654.5:c.451C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-47565132-C-A
• chrX-47565132-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001654.5(ARAF):​c.451C>A​(p.Arg151Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 1.68

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19966197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAF	NM_001654.5	c.451C>A	p.Arg151Ser	missense_variant	Exon 5 of 16	ENST00000377045.9	NP_001645.1
ARAF	NM_001256196.2	c.451C>A	p.Arg151Ser	missense_variant	Exon 5 of 16		NP_001243125.1
ARAF	NM_001256197.2	c.451C>A	p.Arg151Ser	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.451C>A	p.Arg151Ser	missense_variant	Exon 5 of 16	1	NM_001654.5	ENSP00000366244.4
ARAF	ENST00000377039.2	c.451C>A	p.Arg151Ser	missense_variant	Exon 5 of 6	2		ENSP00000366238.1
ARAF	ENST00000489496.1	n.371C>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	Benign	0.18
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T;T;.
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	1.9	.;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.48	N;N;N
REVEL	Uncertain	0.55
Sift	Uncertain	0.019	D;T;D
Sift4G	Benign	0.78	T;T;T
Polyphen		0.043	.;B;.
Vest4		0.44
MutPred		0.44		Loss of catalytic residue at R151 (P = 0.0532);Loss of catalytic residue at R151 (P = 0.0532);Loss of catalytic residue at R151 (P = 0.0532);
MVP		0.96
MPC		0.087
ClinPred		0.15	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.76

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-47424531;