Variant 2-9630205-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000238081.8(YWHAQ):c.248G>C(p.Arg83Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

YWHAQ
ENST00000238081.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

Variant links:

Genes affected

YWHAQ (HGNC:12854): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta) This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse and rat orthologs. This gene is upregulated in patients with amyotrophic lateral sclerosis. It contains in its 5' UTR a 6 bp tandem repeat sequence which is polymorphic, however, there is no correlation between the repeat number and the disease. [provided by RefSeq, Jul 2008]

YWHAQ links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAQ	NM_006826.4 linkuse as main transcript	c.248G>C	p.Arg83Pro	missense_variant	2/6	ENST00000238081.8	NP_006817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
YWHAQ	ENST00000238081.8 linkuse as main transcript	c.248G>C	p.Arg83Pro	missense_variant	2/6	1	NM_006826.4	ENSP00000238081	P1
YWHAQ	ENST00000381844.8 linkuse as main transcript	c.248G>C	p.Arg83Pro	missense_variant	1/5	1		ENSP00000371267	P1
YWHAQ	ENST00000446619.1 linkuse as main transcript	c.248G>C	p.Arg83Pro	missense_variant	2/4	3		ENSP00000398990
YWHAQ	ENST00000460093.1 linkuse as main transcript	n.64G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Dec 27, 2022

The c.248G>C (p.R83P) alteration is located in exon 2 (coding exon 1) of the YWHAQ gene. This alteration results from a G to C substitution at nucleotide position 248, causing the arginine (R) at amino acid position 83 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

D;D;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Benign

0.063

MetaRNN

Pathogenic

0.85

D;D;D

MetaSVM

Uncertain

-0.034

MutationAssessor

Pathogenic

4.3

H;H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.4

D;D;D

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;.

Polyphen

1.0

D;D;.

Vest4

0.90

MutPred

0.71

Gain of ubiquitination at K80 (P = 0.0872);Gain of ubiquitination at K80 (P = 0.0872);Gain of ubiquitination at K80 (P = 0.0872);

MVP

0.68

MPC

2.2

ClinPred

1.0

GERP RS

4.6

Varity_R

0.97

gMVP

0.91

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over