rs12692388

Positions:

• chr2-9614340-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
YWHAQ	NM_006826.4	c.294+15819G>A		intron_variant		ENST00000238081.8	NP_006817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YWHAQ	ENST00000238081.8	c.294+15819G>A		intron_variant		1	NM_006826.4	ENSP00000238081	P1
YWHAQ	ENST00000381844.8	c.294+15819G>A		intron_variant		1		ENSP00000371267	P1
YWHAQ	ENST00000446619.1	c.294+15819G>A		intron_variant		3		ENSP00000398990
YWHAQ	ENST00000474715.1	n.60+6302G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.0581

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.584

Alfa AF: 0.536 Hom.: 12064

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12692388; hg19: chr2-9754469;