rs142304168

Variant names:

• chrX-47567043-G-A
• rs142304168
• NM_001654.5:c.785G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-47567043-G-A
• chrX-47567043-G-C
• chrX-47567043-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001654.5(ARAF):​c.785G>A​(p.Ser262Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S262I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ARAF NM_001654.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 0 publications found

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]

ARAF Gene-Disease associations (from GenCC):

• diffuse lymphatic malformation

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091771364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001654.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAF	NM_001654.5	MANE Select	c.785G>A	p.Ser262Asn	missense	Exon 9 of 16	NP_001645.1	A0A024R178
	ARAF	NM_001256196.2		c.794G>A	p.Ser265Asn	missense	Exon 9 of 16	NP_001243125.1	Q96II5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAF	ENST00000377045.9	TSL:1 MANE Select	c.785G>A	p.Ser262Asn	missense	Exon 9 of 16	ENSP00000366244.4	P10398-1
	ARAF	ENST00000895646.1		c.785G>A	p.Ser262Asn	missense	Exon 9 of 16	ENSP00000565705.1
	ARAF	ENST00000895654.1		c.818G>A	p.Ser273Asn	missense	Exon 9 of 16	ENSP00000565713.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.72
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.056
Sift	Benign	0.30	T
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.18		Loss of phosphorylation at S262 (P = 0.002)
MVP		0.52
MPC		0.071
ClinPred		0.044	T
GERP RS		0.60
Varity_R		0.069
gMVP		0.36
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs142304168; hg19: chrX-47426442;