Variant X-47563255-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001654.5(ARAF):c.126C>T(p.Tyr42Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,096,808 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000026 ( 0 hom. 12 hem. )

Consequence

ARAF
NM_001654.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0540

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant X-47563255-C-T is Benign according to our data. Variant chrX-47563255-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660426.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.054 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAF	NM_001654.5 link	c.126C>T	p.Tyr42Tyr	synonymous_variant	Exon 3 of 16	ENST00000377045.9	NP_001645.1	P10398-1A0A024R178
ARAF	NM_001256196.2 link	c.126C>T	p.Tyr42Tyr	synonymous_variant	Exon 3 of 16		NP_001243125.1	P10398Q96II5
ARAF	NM_001256197.2 link	c.126C>T	p.Tyr42Tyr	synonymous_variant	Exon 3 of 6		NP_001243126.1	P10398-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARAF	ENST00000377045.9 link	c.126C>T	p.Tyr42Tyr	synonymous_variant	Exon 3 of 16	1	NM_001654.5	ENSP00000366244.4	P10398-1
ARAF	ENST00000377039.2 link	c.126C>T	p.Tyr42Tyr	synonymous_variant	Exon 3 of 6	2		ENSP00000366238.1	P10398-2
ARAF	ENST00000489496.1 link	n.46C>T		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000223

AC:

AN:

179653

Hom.:

AF XY:

0.0000310

AC XY:

AN XY:

64433

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000220

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000255

AC:

AN:

1096808

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

362236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000428

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ARAF: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.1

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over