Variant 17-1361136-G-A 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_006761.5(YWHAE):c.534C>T(p.Ser178Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,036 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 4 hom. )

Consequence

YWHAE
NM_006761.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.947

Variant links:

Genes affected

YWHAE (HGNC:12851): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon) 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 100% identical to the mouse ortholog. It interacts with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer. Two transcript variants, one protein-coding and the other non-protein-coding, have been found for this gene. [provided by RefSeq, Aug 2008]

YWHAE links:

YWHAE (HGNC:):

YWHAE links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 17-1361136-G-A is Benign according to our data. Variant chr17-1361136-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 705898.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-1361136-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.947 with no splicing effect.

BS2

High AC in GnomAd4 at 191 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAE	NM_006761.5 linkuse as main transcript	c.534C>T	p.Ser178Ser	synonymous_variant	4/6	ENST00000264335.13	NP_006752.1	P62258-1V9HW98
YWHAE	NR_024058.2 linkuse as main transcript	n.679C>T		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAE	ENST00000264335.13 linkuse as main transcript	c.534C>T	p.Ser178Ser	synonymous_variant	4/6	1	NM_006761.5	ENSP00000264335.8		P62258-1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

192

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000591

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00109

AC:

274

AN:

251450

Hom.:

AF XY:

0.00107

AC XY:

145

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00197

AC:

2881

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1439

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.00240

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00125

AC:

191

AN:

152194

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00241

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.00118

EpiCase

AF:

0.00278

EpiControl

AF:

0.00219

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

YWHAE-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

4.3

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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