rs9393

Variant names:

• chr17-1345098-A-C
• rs9393
• NM_006761.5:c.*349T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-1345098-A-C
• chr17-1345098-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 16 publications found

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

ACMG classification

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAE	NM_006761.5	c.*349T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000264335.13	NP_006752.1
YWHAE	NR_024058.2	n.1262T>G		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAE	ENST00000264335.13	c.*349T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_006761.5	ENSP00000264335.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 182142 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 91970

African (AFR) AF: 0.00 AC: 0 AN: 5868

American (AMR) AF: 0.00 AC: 0 AN: 6930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7260

East Asian (EAS) AF: 0.00 AC: 0 AN: 15650

South Asian (SAS) AF: 0.00 AC: 0 AN: 12386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 888

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 114048

Other (OTH) AF: 0.00 AC: 0 AN: 12110

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 206

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
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

Other links and lift over

dbSNP: rs9393; hg19: chr17-1248392;