17-1361770-A-T

Variant names:

• chr17-1361770-A-T
• rs3752826
• NM_006761.5:c.371+132T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006761.5(YWHAE):​c.371+132T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 438,982 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: YWHAE NM_006761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.371+132T>A		intron	N/A	NP_006752.1
	YWHAE	NR_024058.2		n.516+132T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAE	ENST00000264335.13	TSL:1 MANE Select	c.371+132T>A		intron	N/A	ENSP00000264335.8
	YWHAE	ENST00000571732.5	TSL:1	c.305+132T>A		intron	N/A	ENSP00000461762.1
	YWHAE	ENST00000469398.5	TSL:2	n.577T>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000228 AC: 1 AN: 438982 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 226650

African (AFR) AF: 0.00 AC: 0 AN: 10790

American (AMR) AF: 0.00 AC: 0 AN: 11726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11952

East Asian (EAS) AF: 0.00 AC: 0 AN: 27444

South Asian (SAS) AF: 0.00 AC: 0 AN: 26746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1770

European-Non Finnish (NFE) AF: 0.00000352 AC: 1 AN: 283944

Other (OTH) AF: 0.00 AC: 0 AN: 23580

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.92
DANN	Benign	0.12
PhyloP100		-0.35
PromoterAI		0.0088	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3752826; hg19: chr17-1265064;