17-1345289-T-TA

Variant summary

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

The NM_006761.5(YWHAE):c.*157_*158insT 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 0.052 (302 hom., cov: 0)
  • Exomes 𝑓: 0.16 (37 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-T-TA is Benign according to our data. Variant chr17-1345289-T-TA is described in ClinVar as [Benign]. Clinvar id is 1236952.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAE	NM_006761.5	c.*157_*158insT		3_prime_UTR_variant	6/6	ENST00000264335.13
YWHAE	NR_024058.2	n.1070_1071insT		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAE	ENST00000264335.13	c.*157_*158insT		3_prime_UTR_variant	6/6	1	NM_006761.5	P1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 6537 AN: 126558 Hom.: 299 Cov.: 0

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0506

Gnomad EAS AF: 0.0340

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.0217

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0567

GnomAD4 exome AF: 0.158 AC: 59184 AN: 374854 Hom.: 37 Cov.: 4 AF XY: 0.159 AC XY: 31251 AN XY: 196824

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.0517 AC: 6549 AN: 126556 Hom.: 302 Cov.: 0 AF XY: 0.0534 AC XY: 3227 AN XY: 60446

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0506

Gnomad4 EAS AF: 0.0339

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0544

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0565

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 17, 2021

- -

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;