Variant chr8-100924055-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145690.3(YWHAZ):c.583-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 1,608,646 control chromosomes in the GnomAD database, including 5,481 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 422 hom., cov: 32)

Exomes 𝑓: 0.078 ( 5059 hom. )

Consequence

YWHAZ
NM_145690.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009109

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.262

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 8-100924055-G-A is Benign according to our data. Variant chr8-100924055-G-A is described in ClinVar as [Benign]. Clinvar id is 1555264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAZ	NM_145690.3 linkuse as main transcript	c.583-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000395958.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAZ	ENST00000395958.6 linkuse as main transcript	c.583-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_145690.3	P1	P63104-1

Frequencies

GnomAD3 genomes

AF:

0.0587

AC:

8927

AN:

152040

Hom.:

423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0360

Gnomad ASJ

AF:

0.0478

Gnomad EAS

AF:

0.00385

Gnomad SAS

AF:

0.0680

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0822

Gnomad OTH

AF:

0.0416

GnomAD3 exomes

AF:

0.0676

AC:

16563

AN:

244970

Hom.:

803

AF XY:

0.0704

AC XY:

9327

AN XY:

132410

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.0588

Gnomad EAS exome

AF:

0.000388

Gnomad SAS exome

AF:

0.0717

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.0814

Gnomad OTH exome

AF:

0.0715

GnomAD4 exome

AF:

0.0783

AC:

113976

AN:

1456488

Hom.:

5059

Cov.:

AF XY:

0.0783

AC XY:

56723

AN XY:

724400

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.0256

Gnomad4 ASJ exome

AF:

0.0579

Gnomad4 EAS exome

AF:

0.000580

Gnomad4 SAS exome

AF:

0.0721

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.0831

Gnomad4 OTH exome

AF:

0.0702

GnomAD4 genome

AF:

0.0587

AC:

8926

AN:

152158

Hom.:

422

Cov.:

AF XY:

0.0614

AC XY:

4569

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.0359

Gnomad4 ASJ

AF:

0.0478

Gnomad4 EAS

AF:

0.00366

Gnomad4 SAS

AF:

0.0683

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.0822

Gnomad4 OTH

AF:

0.0417

Alfa

AF:

0.0718

Hom.:

218

Bravo

AF:

0.0469

Asia WGS

AF:

0.0320

AC:

110

AN:

3478

EpiCase

AF:

0.0747

EpiControl

AF:

0.0734

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

YWHAZ-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.1

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over