rs933226

chr22-31947860-T-C

Variant summary

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

The NM_003405.4(YWHAH):c.87+3040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,222 control chromosomes in the GnomAD database, including 1,738 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 0.14 (1738 hom., cov: 33)
• Consequence: YWHAH NM_003405.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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]

LOC124900477 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAH	NM_003405.4	c.87+3040T>C		intron_variant		ENST00000248975.6
LOC124900477	XR_007068065.1	n.978T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAH	ENST00000248975.6	c.87+3040T>C		intron_variant		1	NM_003405.4	P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20659 AN: 152104 Hom.: 1736 Cov.: 33

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.136 AC: 20662 AN: 152222 Hom.: 1738 Cov.: 33 AF XY: 0.137 AC XY: 10226 AN XY: 74424

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0907

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.124

Alfa AF: 0.152 Hom.: 325

Bravo AF: 0.124

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.8
Dann	Benign	0.82

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: rs933226; hg19: chr22-32343847;