17-1361317-TA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006761.5(YWHAE):c.372-20del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (16482 hom., cov: 0)
  • Exomes 𝑓: 0.40 (11465 hom.)
  • Failed GnomAD Quality Control
• Consequence: YWHAE NM_006761.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.265

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 -16 ACMG points.

• BP6: Variant 17-1361317-TA-T is Benign according to our data. Variant chr17-1361317-TA-T is described in ClinVar as [Benign]. Clinvar id is 1226644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-1361317-TA-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAE	NM_006761.5	c.372-20del		intron_variant		ENST00000264335.13
YWHAE	NR_024058.2	n.517-20del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAE	ENST00000264335.13	c.372-20del		intron_variant		1	NM_006761.5	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 69770 AN: 144040 Hom.: 16457 Cov.: 0

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.484

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.398 AC: 470342 AN: 1180578 Hom.: 11465 Cov.: 0 AF XY: 0.400 AC XY: 234496 AN XY: 586250

Gnomad4 AFR exome AF: 0.431

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.404

GnomAD4 genome AF: 0.485 AC: 69849 AN: 144124 Hom.: 16482 Cov.: 0 AF XY: 0.490 AC XY: 34262 AN XY: 69906

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.487

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 11, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 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: rs55734488; hg19: chr17-1264611;