rs12692388

Variant names:

• chr2-9614340-C-T
• rs12692388
• NM_006826.4:c.294+15819G>A

Variant summary

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

The NM_006826.4(YWHAQ):​c.294+15819G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,116 control chromosomes in the GnomAD database, including 27,667 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 0.58 (27667 hom., cov: 33)
• Consequence: YWHAQ NM_006826.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595
• Publications: 2 publications found

Genes affected

YWHAQ (HGNC:12854): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta) 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 and rat orthologs. This gene is upregulated in patients with amyotrophic lateral sclerosis. It contains in its 5' UTR a 6 bp tandem repeat sequence which is polymorphic, however, there is no correlation between the repeat number and the disease. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YWHAQ	NM_006826.4	c.294+15819G>A		intron_variant	Intron 2 of 5	ENST00000238081.8	NP_006817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YWHAQ	ENST00000238081.8	c.294+15819G>A		intron_variant	Intron 2 of 5	1	NM_006826.4	ENSP00000238081.3
YWHAQ	ENST00000381844.8	c.294+15819G>A		intron_variant	Intron 1 of 4	1		ENSP00000371267.4
YWHAQ	ENST00000446619.1	c.294+15819G>A		intron_variant	Intron 2 of 3	3		ENSP00000398990.1
YWHAQ	ENST00000474715.1	n.60+6302G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87673 AN: 151998 Hom.: 27628 Cov.: 33

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.0582

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.577 AC: 87765 AN: 152116 Hom.: 27667 Cov.: 33 AF XY: 0.565 AC XY: 42047 AN XY: 74356

African (AFR) AF: 0.804 AC: 33376 AN: 41522

American (AMR) AF: 0.423 AC: 6464 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2190 AN: 3470

East Asian (EAS) AF: 0.0581 AC: 301 AN: 5180

South Asian (SAS) AF: 0.380 AC: 1837 AN: 4830

European-Finnish (FIN) AF: 0.510 AC: 5382 AN: 10562

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36328 AN: 67960

Other (OTH) AF: 0.584 AC: 1232 AN: 2108

Alfa AF: 0.539 Hom.: 13480

Bravo AF: 0.580

Asia WGS AF: 0.297 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.76
PhyloP100		-0.59
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: rs12692388; hg19: chr2-9754469;