dbSNP rs9393: YWHAE:c.*349T>G (chr17-1345098-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006761.5(YWHAE):c.*349T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

YWHAE
NM_006761.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.31

Publications

16 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:

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new If you want to explore the variant's impact on the transcript NM_006761.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006761.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAE	NM_006761.5	MANE Select	c.*349T>G		3_prime_UTR	Exon 6 of 6	NP_006752.1	P62258-1
	YWHAE	NR_024058.2		n.1262T>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YWHAE	ENST00000264335.13	TSL:1 MANE Select	c.*349T>G	3_prime_UTR	Exon 6 of 6	ENSP00000264335.8	P62258-1
YWHAE	ENST00000571732.5	TSL:1	c.*349T>G	3_prime_UTR	Exon 7 of 7	ENSP00000461762.1	P62258-2
YWHAE	ENST00000928923.1		c.*349T>G	3_prime_UTR	Exon 6 of 6	ENSP00000598982.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

182142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

91970

African (AFR)

AF:

0.00

AC:

AN:

5868

American (AMR)

AF:

0.00

AC:

AN:

6930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7260

East Asian (EAS)

AF:

0.00

AC:

AN:

15650

South Asian (SAS)

AF:

0.00

AC:

AN:

12386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

888

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

114048

Other (OTH)

AF:

0.00

AC:

AN:

12110

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

206

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over