17-1345289-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006761.5(YWHAE):c.*157del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (50 hom., cov: 0)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: YWHAE NM_006761.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.300

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-1345289-TA-T is Benign according to our data. Variant chr17-1345289-TA-T is described in ClinVar as [Benign]. Clinvar id is 1269526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAE	NM_006761.5	c.*157del		3_prime_UTR_variant	6/6	ENST00000264335.13
YWHAE	NR_024058.2	n.1070del		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAE	ENST00000264335.13	c.*157del		3_prime_UTR_variant	6/6	1	NM_006761.5	P1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 2599 AN: 126542 Hom.: 50 Cov.: 0

Gnomad AFR AF: 0.0650

Gnomad AMI AF: 0.00133

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.000314

Gnomad EAS AF: 0.00583

Gnomad SAS AF: 0.00252

Gnomad FIN AF: 0.00325

Gnomad MID AF: 0.0145

Gnomad NFE AF: 0.00283

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.106 AC: 39453 AN: 372684 Hom.: 0 Cov.: 4 AF XY: 0.106 AC XY: 20696 AN XY: 195804

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.0970

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0901

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0206 AC: 2609 AN: 126538 Hom.: 50 Cov.: 0 AF XY: 0.0205 AC XY: 1238 AN XY: 60436

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.00843

Gnomad4 ASJ AF: 0.000314

Gnomad4 EAS AF: 0.00585

Gnomad4 SAS AF: 0.00253

Gnomad4 FIN AF: 0.00325

Gnomad4 NFE AF: 0.00285

Gnomad4 OTH AF: 0.0138

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs566935846; hg19: chr17-1248583;