8-100931176-A-C

Position:

• chr8-100931176-A-C

Variant summary

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

The NM_145690.3(YWHAZ):​c.295-6137T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 152,310 control chromosomes in the GnomAD database, including 301 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 0.060 (301 hom., cov: 33)
• Consequence: YWHAZ NM_145690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAZ	NM_145690.3	c.295-6137T>G		intron_variant		ENST00000395958.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAZ	ENST00000395958.6	c.295-6137T>G		intron_variant		1	NM_145690.3	P1

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9177 AN: 152192 Hom.: 293 Cov.: 33

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0460

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0597

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

GnomAD4 genome AF: 0.0604 AC: 9205 AN: 152310 Hom.: 301 Cov.: 33 AF XY: 0.0584 AC XY: 4351 AN XY: 74492

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.0148

Gnomad4 SAS AF: 0.0375

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0580

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0573 Hom.: 337

Bravo AF: 0.0610

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.98
DANN	Benign	0.45

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: rs17365661; hg19: chr8-101943404;