X-47566731-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001654.5(ARAF):āc.650A>Gā(p.Asn217Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000913 in 1,095,397 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 22)
Exomes š: 9.1e-7 ( 0 hom. 1 hem. )
Consequence
ARAF
NM_001654.5 missense
NM_001654.5 missense
Scores
2
9
6
Clinical Significance
Conservation
PhyloP100: 7.18
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]
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ACMG classification
Classification made for transcript
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARAF | NM_001654.5 | c.650A>G | p.Asn217Ser | missense_variant | 7/16 | ENST00000377045.9 | |
ARAF | NM_001256196.2 | c.659A>G | p.Asn220Ser | missense_variant | 7/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARAF | ENST00000377045.9 | c.650A>G | p.Asn217Ser | missense_variant | 7/16 | 1 | NM_001654.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1095397Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 1AN XY: 361163
GnomAD4 exome
AF:
AC:
1
AN:
1095397
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
361163
Gnomad4 AFR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 14, 2023 | The c.650A>G (p.N217S) alteration is located in exon 7 (coding exon 6) of the ARAF gene. This alteration results from a A to G substitution at nucleotide position 650, causing the asparagine (N) at amino acid position 217 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;D
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D
REVEL
Uncertain
Sift
Benign
.;T
Sift4G
Benign
T;T
Polyphen
0.88
.;P
Vest4
MutPred
0.25
.;Loss of loop (P = 0.0203);
MVP
MPC
0.14
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.