17-1345098-A-G

Variant names:

• chr17-1345098-A-G
• rs9393
• NM_006761.5:c.*349T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

YWHAE Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006761.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAE	NM_006761.5	MANE Select	c.*349T>C		3_prime_UTR	Exon 6 of 6	NP_006752.1
	YWHAE	NR_024058.2		n.1262T>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAE	ENST00000264335.13	TSL:1 MANE Select	c.*349T>C		3_prime_UTR	Exon 6 of 6	ENSP00000264335.8
	YWHAE	ENST00000571732.5	TSL:1	c.*349T>C		3_prime_UTR	Exon 7 of 7	ENSP00000461762.1
	YWHAE	ENST00000466227.6	TSL:5	n.*489T>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000464883.1

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

African (AFR) AF: 0.156 AC: 911 AN: 5858

American (AMR) AF: 0.272 AC: 1884 AN: 6920

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 549 AN: 7258

East Asian (EAS) AF: 0.252 AC: 3942 AN: 15634

South Asian (SAS) AF: 0.0619 AC: 767 AN: 12382

European-Finnish (FIN) AF: 0.0858 AC: 600 AN: 6990

Middle Eastern (MID) AF: 0.0687 AC: 61 AN: 888

European-Non Finnish (NFE) AF: 0.0759 AC: 8645 AN: 113950

Other (OTH) AF: 0.0937 AC: 1133 AN: 12094

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

African (AFR) AF: 0.162 AC: 6696 AN: 41448

American (AMR) AF: 0.238 AC: 3639 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 255 AN: 3468

East Asian (EAS) AF: 0.180 AC: 935 AN: 5182

South Asian (SAS) AF: 0.0700 AC: 338 AN: 4830

European-Finnish (FIN) AF: 0.0839 AC: 888 AN: 10590

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0791 AC: 5381 AN: 67986

Other (OTH) AF: 0.132 AC: 279 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9393; hg19: chr17-1248392;