17-1361318-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006761.5(YWHAE):c.372-20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00072 (0 hom.)
• Consequence: YWHAE NM_006761.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-1361318-A-T is Benign according to our data. Variant chr17-1361318-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2772722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000564 AC: 14 AN: 24816 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00118

Gnomad FIN AF: 0.000825

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000789

Gnomad OTH AF: 0.00292

GnomAD4 exome AF: 0.000724 AC: 87 AN: 120206 Hom.: 0 Cov.: 0 AF XY: 0.000822 AC XY: 48 AN XY: 58362

Gnomad4 AFR exome AF: 0.000603

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000593

Gnomad4 EAS exome AF: 0.00178

Gnomad4 SAS exome AF: 0.00259

Gnomad4 FIN exome AF: 0.00133

Gnomad4 NFE exome AF: 0.000622

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.000564 AC: 14 AN: 24804 Hom.: 0 Cov.: 0 AF XY: 0.000337 AC XY: 4 AN XY: 11858

Gnomad4 AFR AF: 0.000282

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00118

Gnomad4 FIN AF: 0.000825

Gnomad4 NFE AF: 0.000790

Gnomad4 OTH AF: 0.00292

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 01, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.51
Dann	Benign	0.41

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: rs202084215; hg19: chr17-1264612;