17-1361317-T-TA

Variant summary

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

The NM_006761.5(YWHAE):c.372-20_372-19insT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (951 hom., cov: 0)
  • Exomes 𝑓: 0.13 (371 hom.)
• 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-T-TA is Benign according to our data. Variant chr17-1361317-T-TA is described in ClinVar as [Benign]. Clinvar id is 1246571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAE	NM_006761.5	c.372-20_372-19insT		intron_variant		ENST00000264335.13
YWHAE	NR_024058.2	n.517-20_517-19insT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAE	ENST00000264335.13	c.372-20_372-19insT		intron_variant		1	NM_006761.5	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 16219 AN: 144060 Hom.: 951 Cov.: 0

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00977

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0940

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.130 AC: 156064 AN: 1198016 Hom.: 371 Cov.: 0 AF XY: 0.127 AC XY: 75832 AN XY: 595080

Gnomad4 AFR exome AF: 0.0849

Gnomad4 AMR exome AF: 0.0581

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0187

Gnomad4 SAS exome AF: 0.0740

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.113 AC: 16221 AN: 144146 Hom.: 951 Cov.: 0 AF XY: 0.109 AC XY: 7628 AN XY: 69908

Gnomad4 AFR AF: 0.0846

Gnomad4 AMR AF: 0.0855

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.0643

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.109

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	GeneDx	May 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 04, 2023	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;