chr8-100946205-G-T

Variant names:

• chr8-100946205-G-T
• rs3134358
• NM_145690.3:c.294+2391C>A

Variant summary

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

The NM_145690.3(YWHAZ):​c.294+2391C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,992 control chromosomes in the GnomAD database, including 33,194 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 (33194 hom., cov: 31)
• Consequence: YWHAZ NM_145690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 7 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 (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.294+2391C>A		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.294+2391C>A		intron_variant	Intron 2 of 5	1	NM_145690.3	ENSP00000379288.2

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99556 AN: 151876 Hom.: 33163 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.655 AC: 99630 AN: 151992 Hom.: 33194 Cov.: 31 AF XY: 0.651 AC XY: 48370 AN XY: 74278

African (AFR) AF: 0.785 AC: 32570 AN: 41490

American (AMR) AF: 0.627 AC: 9583 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2155 AN: 3468

East Asian (EAS) AF: 0.636 AC: 3274 AN: 5148

South Asian (SAS) AF: 0.696 AC: 3350 AN: 4816

European-Finnish (FIN) AF: 0.515 AC: 5426 AN: 10540

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41186 AN: 67938

Other (OTH) AF: 0.641 AC: 1350 AN: 2106

Alfa AF: 0.643 Hom.: 4811

Bravo AF: 0.670

Asia WGS AF: 0.644 AC: 2242 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	1.9
DANN	Benign	0.52
PhyloP100		0.22
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: rs3134358; hg19: chr8-101958433;