rs3105452

Variant names:

• chr8-100931390-A-C
• rs3105452
• NM_145690.3:c.295-6351T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-100931390-A-C
• chr8-100931390-A-G
• chr8-100931390-A-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_145690.3(YWHAZ):​c.295-6351T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 151,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 31)
• Consequence: YWHAZ NM_145690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAZ	NM_145690.3	c.295-6351T>G		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.295-6351T>G		intron_variant	Intron 2 of 5	1	NM_145690.3	ENSP00000379288.2

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 151890 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000112 AC: 17 AN: 151890 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74150

African (AFR) AF: 0.0000726 AC: 3 AN: 41334

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000401 Hom.: 5971

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.9
DANN	Benign	0.71
PhyloP100		0.64

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: rs3105452; hg19: chr8-101943618;