X-47566652-C-A

Variant names:

• chrX-47566652-C-A
• NM_001654.5:c.571C>A

Variant summary

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

The NM_001654.5(ARAF):​c.571C>A​(p.His191Asn) 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. 13/20 in silico tools predict 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: 22)
• Consequence: ARAF NM_001654.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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=0.10464889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAF	NM_001654.5	c.571C>A	p.His191Asn	missense_variant	Exon 7 of 16	ENST00000377045.9	NP_001645.1
ARAF	NM_001256196.2	c.580C>A	p.His194Asn	missense_variant	Exon 7 of 16		NP_001243125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAF	ENST00000377045.9	c.571C>A	p.His191Asn	missense_variant	Exon 7 of 16	1	NM_001654.5	ENSP00000366244.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.84
DEOGEN2	Benign	0.26	T;T
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.0	.;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.10
Sift	Benign	0.36	.;T
Sift4G	Benign	0.31	T;T
Polyphen		0.037	.;B
Vest4		0.17
MutPred		0.14		.;Loss of catalytic residue at H191 (P = 0.0269);
MVP		0.71
MPC		0.082
ClinPred		0.073	T
GERP RS		2.4
Varity_R		0.13
gMVP		0.36

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-47426051;