chr8-100932331-T-A

Variant names:

• chr8-100932331-T-A
• rs3100053
• NM_145690.3:c.295-7292A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

YWHAZ Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics, Illumina

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
YWHAZ	NM_145690.3	c.295-7292A>T		intron_variant	Intron 2 of 5	ENST00000395958.6	NP_663723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAZ	ENST00000395958.6	c.295-7292A>T		intron_variant	Intron 2 of 5	1	NM_145690.3	ENSP00000379288.2

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

African (AFR) AF: 0.333 AC: 13818 AN: 41436

American (AMR) AF: 0.507 AC: 7745 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3466

East Asian (EAS) AF: 0.621 AC: 3208 AN: 5162

South Asian (SAS) AF: 0.630 AC: 3032 AN: 4812

European-Finnish (FIN) AF: 0.446 AC: 4701 AN: 10532

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34626 AN: 67942

Other (OTH) AF: 0.474 AC: 1001 AN: 2114

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
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3100053; hg19: chr8-101944559;