22-31953076-T-C

Variant names:

• chr22-31953076-T-C
• rs2246704
• NM_003405.4:c.88-3063T>C

Variant summary

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

The NM_003405.4(YWHAH):​c.88-3063T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,124 control chromosomes in the GnomAD database, including 14,038 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 0.42 (14038 hom., cov: 32)
• Consequence: YWHAH NM_003405.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 8 publications found

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]

ENSG00000285404 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003405.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAH	NM_003405.4	MANE Select	c.88-3063T>C		intron	N/A	NP_003396.1	Q04917

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAH	ENST00000248975.6	TSL:1 MANE Select	c.88-3063T>C		intron	N/A	ENSP00000248975.5	Q04917
	ENSG00000285404	ENST00000646701.1		c.1787-3063T>C		intron	N/A	ENSP00000496158.1	A0A2R8YF50
	YWHAH	ENST00000946727.1		c.297+2654T>C		intron	N/A	ENSP00000616786.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64293 AN: 152006 Hom.: 14016 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.423 AC: 64357 AN: 152124 Hom.: 14038 Cov.: 32 AF XY: 0.417 AC XY: 31028 AN XY: 74382

African (AFR) AF: 0.490 AC: 20343 AN: 41500

American (AMR) AF: 0.405 AC: 6192 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3470

East Asian (EAS) AF: 0.146 AC: 756 AN: 5184

South Asian (SAS) AF: 0.361 AC: 1739 AN: 4816

European-Finnish (FIN) AF: 0.372 AC: 3935 AN: 10566

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28630 AN: 67980

Other (OTH) AF: 0.398 AC: 840 AN: 2110

Alfa AF: 0.418 Hom.: 22498

Bravo AF: 0.426

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.99
DANN	Benign	0.38
PhyloP100		-0.73
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: rs2246704; hg19: chr22-32349063;