rs17365948

chr8-100944649-C-T

Variant summary

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

The NM_145690.3(YWHAZ):c.294+3947G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 152,238 control chromosomes in the GnomAD database, including 147 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 0.040 (147 hom., cov: 32)
• Consequence: YWHAZ NM_145690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAZ	NM_145690.3	c.294+3947G>A		intron_variant		ENST00000395958.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAZ	ENST00000395958.6	c.294+3947G>A		intron_variant		1	NM_145690.3	P1

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 6044 AN: 152120 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0397 AC: 6045 AN: 152238 Hom.: 147 Cov.: 32 AF XY: 0.0385 AC XY: 2864 AN XY: 74428

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0355

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.0502

Gnomad4 NFE AF: 0.0574

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0453 Hom.: 37

Bravo AF: 0.0373

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	1.8
Dann	Benign	0.74

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: rs17365948; hg19: chr8-101956877;