8-100924013-CTTAATGTA-TACAAAGCGTGCTGTCTTTGTATGAACTCT

Position:

• chr8-100924013-CTTAATGTA-TACAAAGCGTGCTGTCTTTGTATGAACTCT

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PM4 PP3

The NM_145690.3(YWHAZ):​c.612_620delinsAGAGTTCATACAAAGACAGCACGCTTTGTA​(p.Asp204_Ser207delinsGluGluPheIleGlnArgGlnHisAlaLeuTyr) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: YWHAZ NM_145690.3 protein_altering
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32

Genes affected

YWHAZ (HGNC:12855): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) 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 99% identical to the mouse, rat and sheep orthologs. The encoded protein interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. Several transcript variants that differ in the 5' UTR but that encode the same protein have been identified for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a chain 14-3-3 protein zeta/delta (size 244) in uniprot entity 1433Z_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_145690.3
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_145690.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAZ	NM_145690.3	c.612_620delinsAGAGTTCATACAAAGACAGCACGCTTTGTA	p.Asp204_Ser207delinsGluGluPheIleGlnArgGlnHisAlaLeuTyr	protein_altering_variant	5/6	ENST00000395958.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAZ	ENST00000395958.6	c.612_620delinsAGAGTTCATACAAAGACAGCACGCTTTGTA	p.Asp204_Ser207delinsGluGluPheIleGlnArgGlnHisAlaLeuTyr	protein_altering_variant	5/6	1	NM_145690.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-101936241;