NM_006761.5:c.282G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006761.5(YWHAE):c.282G>A(p.Lys94Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,585,946 control chromosomes in the GnomAD database, including 824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 48 hom., cov: 31)

Exomes 𝑓: 0.030 ( 776 hom. )

Consequence

YWHAE
NM_006761.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.193

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

YWHAE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 17-1361991-C-T is Benign according to our data. Variant chr17-1361991-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.193 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.023 (3481/151374) while in subpopulation NFE AF = 0.0348 (2365/67966). AF 95% confidence interval is 0.0336. There are 48 homozygotes in GnomAd4. There are 1596 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 3481 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAE	NM_006761.5 link	c.282G>A	p.Lys94Lys	synonymous_variant	Exon 3 of 6	ENST00000264335.13	NP_006752.1
YWHAE	NR_024058.2 link	n.427G>A		non_coding_transcript_exon_variant	Exon 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAE	ENST00000264335.13 link	c.282G>A	p.Lys94Lys	synonymous_variant	Exon 3 of 6	1	NM_006761.5	ENSP00000264335.8

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3483

AN:

151256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00662

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0305

Gnomad FIN

AF:

0.0178

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0348

Gnomad OTH

AF:

0.0208

GnomAD2 exomes

AF:

0.0237

AC:

5358

AN:

225938

AF XY:

0.0254

show subpopulations

Gnomad AFR exome

AF:

0.00533

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.0319

Gnomad OTH exome

AF:

0.0259

GnomAD4 exome

AF:

0.0302

AC:

43357

AN:

1434572

Hom.:

776

Cov.:

AF XY:

0.0309

AC XY:

22031

AN XY:

713542

show subpopulations

African (AFR)

AF:

0.00474

AC:

152

AN:

32044

American (AMR)

AF:

0.0139

AC:

523

AN:

37580

Ashkenazi Jewish (ASJ)

AF:

0.0240

AC:

604

AN:

25188

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39214

South Asian (SAS)

AF:

0.0346

AC:

2767

AN:

79892

European-Finnish (FIN)

AF:

0.0165

AC:

875

AN:

52960

Middle Eastern (MID)

AF:

0.0371

AC:

208

AN:

5612

European-Non Finnish (NFE)

AF:

0.0332

AC:

36643

AN:

1102984

Other (OTH)

AF:

0.0268

AC:

1584

AN:

59098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

1791

3581

5372

7162

8953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1378

2756

4134

5512

6890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0230

AC:

3481

AN:

151374

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1596

AN XY:

74028

show subpopulations

African (AFR)

AF:

0.00660

AC:

270

AN:

40924

American (AMR)

AF:

0.0226

AC:

344

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0301

AC:

145

AN:

4810

European-Finnish (FIN)

AF:

0.0178

AC:

187

AN:

10498

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0348

AC:

2365

AN:

67966

Other (OTH)

AF:

0.0205

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

167

334

501

668

835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0285

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

8.2

(source)

DANN

Benign

0.56

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over