8-100919206-A-G

Position:

• chr8-100919206-A-G

Variant summary

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

The NM_145690.3(YWHAZ):​c.*1487T>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 0.0458 in 152,620 control chromosomes in the GnomAD database, including 171 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 0.046 (170 hom., cov: 31)
  • Exomes 𝑓: 0.037 (1 hom.)
• Consequence: YWHAZ NM_145690.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YWHAZ	NM_145690.3	c.*1487T>C		3_prime_UTR_variant	6/6	ENST00000395958.6	NP_663723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAZ	ENST00000395958	c.*1487T>C		3_prime_UTR_variant	6/6	1	NM_145690.3	ENSP00000379288.2

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6966 AN: 152182 Hom.: 168 Cov.: 31

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.0375 AC: 12 AN: 320 Hom.: 1 Cov.: 0 AF XY: 0.0361 AC XY: 7 AN XY: 194

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.0323

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0458 AC: 6972 AN: 152300 Hom.: 170 Cov.: 31 AF XY: 0.0444 AC XY: 3309 AN XY: 74470

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.0501

Gnomad4 NFE AF: 0.0575

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0141 Hom.: 8

Bravo AF: 0.0445

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.8
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11551356; hg19: chr8-101931434;