17-1345098-A-G

Position:

• chr17-1345098-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006761.5(YWHAE):​c.*349T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 334,050 control chromosomes in the GnomAD database, including 2,807 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1473 hom., cov: 31)
  • Exomes 𝑓: 0.10 (1334 hom.)
• Consequence: YWHAE NM_006761.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAE	NM_006761.5	c.*349T>C		3_prime_UTR_variant	6/6	ENST00000264335.13
YWHAE	NR_024058.2	n.1262T>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAE	ENST00000264335.13	c.*349T>C		3_prime_UTR_variant	6/6	1	NM_006761.5	P1
YWHAE	ENST00000571732.5	c.*349T>C		3_prime_UTR_variant	7/7	1
YWHAE	ENST00000573026.1	c.*349T>C		3_prime_UTR_variant	2/2	3
YWHAE	ENST00000466227.6	c.*489T>C		3_prime_UTR_variant, NMD_transcript_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18558 AN: 151958 Hom.: 1466 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0792

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.102 AC: 18492 AN: 181974 Hom.: 1334 Cov.: 0 AF XY: 0.0994 AC XY: 9132 AN XY: 91894

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.0756

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.0619

Gnomad4 FIN exome AF: 0.0858

Gnomad4 NFE exome AF: 0.0759

Gnomad4 OTH exome AF: 0.0937

GnomAD4 genome AF: 0.122 AC: 18582 AN: 152076 Hom.: 1473 Cov.: 31 AF XY: 0.124 AC XY: 9233 AN XY: 74340

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.0735

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.0839

Gnomad4 NFE AF: 0.0791

Gnomad4 OTH AF: 0.132

Alfa AF: 0.0886 Hom.: 206

Bravo AF: 0.137

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9393; hg19: chr17-1248392;