Variant rs3752827 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006761.5(YWHAE):c.265-23A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,413,312 control chromosomes in the GnomAD database, including 85,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.36 ( 9941 hom., cov: 31)

Exomes 𝑓: 0.35 ( 75809 hom. )

Consequence

YWHAE
NM_006761.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.564

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-1362031-T-A is Benign according to our data. Variant chr17-1362031-T-A is described in ClinVar as [Benign]. Clinvar id is 260033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAE	NM_006761.5 linkuse as main transcript	c.265-23A>T		intron_variant		ENST00000264335.13	NP_006752.1	P62258-1V9HW98
YWHAE	NR_024058.2 linkuse as main transcript	n.410-23A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAE	ENST00000264335.13 linkuse as main transcript	c.265-23A>T		intron_variant		1	NM_006761.5	ENSP00000264335.8		P62258-1

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54044

AN:

151740

Hom.:

9916

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.370

GnomAD3 exomes

AF:

0.384

AC:

63515

AN:

165272

Hom.:

12443

AF XY:

0.377

AC XY:

34707

AN XY:

92100

show subpopulations

Gnomad AFR exome

AF:

0.345

Gnomad AMR exome

AF:

0.601

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.402

Gnomad SAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.377

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.348

AC:

439351

AN:

1261454

Hom.:

75809

Cov.:

AF XY:

0.347

AC XY:

219141

AN XY:

631374

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.580

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.361

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.356

AC:

54123

AN:

151858

Hom.:

9941

Cov.:

AF XY:

0.361

AC XY:

26790

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.334

Gnomad4 AMR

AF:

0.509

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.372

Gnomad4 SAS

AF:

0.324

Gnomad4 FIN

AF:

0.355

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.345

Hom.:

1748

Bravo

AF:

0.366

Asia WGS

AF:

0.360

AC:

1253

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.012

DANN

Benign

0.32

BranchPoint Hunter

1.0

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

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