17-1361317-T-A

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.372-19A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00947 in 1,358,758 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (6 hom., cov: 25)
  • Exomes 𝑓: 0.0099 (19 hom.)
• Consequence: YWHAE NM_006761.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.836

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=-0.88).
• BP6: Variant 17-1361317-T-A is Benign according to our data. Variant chr17-1361317-T-A is described in ClinVar as [Benign]. Clinvar id is 1600109.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-1361317-T-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 898 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00623 AC: 898 AN: 144174 Hom.: 6 Cov.: 25

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00587

Gnomad ASJ AF: 0.0244

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00284

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00957

Gnomad OTH AF: 0.00700

GnomAD4 exome AF: 0.00985 AC: 11964 AN: 1214498 Hom.: 19 Cov.: 21 AF XY: 0.00971 AC XY: 5859 AN XY: 603414

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.00280

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00389

Gnomad4 FIN exome AF: 0.00275

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.00896

GnomAD4 genome AF: 0.00623 AC: 899 AN: 144260 Hom.: 6 Cov.: 25 AF XY: 0.00609 AC XY: 426 AN XY: 69970

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00586

Gnomad4 ASJ AF: 0.0244

Gnomad4 EAS AF: 0.000204

Gnomad4 SAS AF: 0.00307

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00957

Gnomad4 OTH AF: 0.00692

Alfa AF: 0.00961 Hom.: 0

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

Invitae

Jan 11, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.92
Dann	Benign	0.19

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: rs556044563; hg19: chr17-1264611;