17-1345289-T-TAA

Variant summary

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

The NM_006761.5(YWHAE):c.*157_*158insTT 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 0.29 (4733 hom., cov: 0)
  • Exomes 𝑓: 0.17 (492 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-TAA is Benign according to our data. Variant chr17-1345289-T-TAA is described in ClinVar as [Benign]. Clinvar id is 1248679.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAE	NM_006761.5	c.*157_*158insTT		3_prime_UTR_variant	6/6	ENST00000264335.13
YWHAE	NR_024058.2	n.1070_1071insTT		non_coding_transcript_exon_variant	7/7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.285 AC: 35992 AN: 126244 Hom.: 4733 Cov.: 0

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.174 AC: 64585 AN: 370622 Hom.: 492 Cov.: 4 AF XY: 0.175 AC XY: 34022 AN XY: 194556

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.285 AC: 35995 AN: 126240 Hom.: 4733 Cov.: 0 AF XY: 0.287 AC XY: 17297 AN XY: 60240

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.278

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

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Computational scores

Source: dbNSFP v4.3

Splicing

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;