rs3100053

chr8-100932331-T-A

Variant summary

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

The NM_145690.3(YWHAZ):c.295-7292A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,948 control chromosomes in the GnomAD database, including 17,013 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 0.46 (17013 hom., cov: 31)
• Consequence: YWHAZ NM_145690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAZ	NM_145690.3	c.295-7292A>T		intron_variant		ENST00000395958.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAZ	ENST00000395958.6	c.295-7292A>T		intron_variant		1	NM_145690.3	P1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70558 AN: 151830 Hom.: 17019 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.464 AC: 70570 AN: 151948 Hom.: 17013 Cov.: 31 AF XY: 0.467 AC XY: 34662 AN XY: 74232

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.474

Alfa AF: 0.482 Hom.: 2233

Bravo AF: 0.463

Asia WGS AF: 0.576 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.1
Dann	Benign	0.36

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: rs3100053; hg19: chr8-101944559;