rs983583

Variant names:

• chr8-100949682-T-C
• rs983583
• NM_145690.3:c.-11-782A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145690.3(YWHAZ):​c.-11-782A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,062 control chromosomes in the GnomAD database, including 33,265 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 0.66 (33265 hom., cov: 32)
• Consequence: YWHAZ NM_145690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAZ	NM_145690.3	c.-11-782A>G		intron_variant	Intron 1 of 5	ENST00000395958.6	NP_663723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAZ	ENST00000395958.6	c.-11-782A>G		intron_variant	Intron 1 of 5	1	NM_145690.3	ENSP00000379288.2

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99683 AN: 151944 Hom.: 33234 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.656 AC: 99757 AN: 152062 Hom.: 33265 Cov.: 32 AF XY: 0.652 AC XY: 48462 AN XY: 74342

African (AFR) AF: 0.786 AC: 32581 AN: 41474

American (AMR) AF: 0.627 AC: 9583 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2165 AN: 3470

East Asian (EAS) AF: 0.636 AC: 3297 AN: 5182

South Asian (SAS) AF: 0.700 AC: 3376 AN: 4824

European-Finnish (FIN) AF: 0.516 AC: 5445 AN: 10560

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41221 AN: 67954

Other (OTH) AF: 0.642 AC: 1352 AN: 2106

Alfa AF: 0.632 Hom.: 15630

Bravo AF: 0.670

Asia WGS AF: 0.646 AC: 2248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		-1.8
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: rs983583; hg19: chr8-101961910;