rs1049583

chr22-31956804-G-Achr22-31956804-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003405.4(YWHAH):c.*12G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,565,662 control chromosomes in the GnomAD database, including 74,632 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 0.24 (5418 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69214 hom.)
• Consequence: YWHAH NM_003405.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

Genes affected

YWHAH (HGNC:12853): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta) 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 bovine orthologs. This gene contains a 7 bp repeat sequence in its 5' UTR, and changes in the number of this repeat have been associated with early-onset schizophrenia and psychotic bipolar disorder. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAH	NM_003405.4	c.*12G>A		3_prime_UTR_variant	2/2	ENST00000248975.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAH	ENST00000248975.6	c.*12G>A		3_prime_UTR_variant	2/2	1	NM_003405.4	P1
YWHAH	ENST00000397492.1	c.*649G>A		3_prime_UTR_variant	3/3	3
YWHAH	ENST00000471374.1	n.936G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36484 AN: 151980 Hom.: 5411 Cov.: 32

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.256

GnomAD3 exomes AF: 0.291 AC: 53306 AN: 183110 Hom.: 8120 AF XY: 0.296 AC XY: 28757 AN XY: 97304

Gnomad AFR exome AF: 0.0690

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.154

Gnomad SAS exome AF: 0.290

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.308 AC: 434890 AN: 1413564 Hom.: 69214 Cov.: 34 AF XY: 0.307 AC XY: 214767 AN XY: 698720

Gnomad4 AFR exome AF: 0.0635

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.326

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.240 AC: 36503 AN: 152098 Hom.: 5418 Cov.: 32 AF XY: 0.242 AC XY: 18002 AN XY: 74366

Gnomad4 AFR AF: 0.0718

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.258

Alfa AF: 0.236 Hom.: 1261

Bravo AF: 0.230

Asia WGS AF: 0.220 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	13
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1049583; hg19: chr22-32352791; COSMIC: COSV50708718; COSMIC: COSV50708718;