dbSNP rs11539379: YWHAH:c.-22G>T (chr22-31944712-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003405.4(YWHAH):c.-22G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000816 in 1,225,290 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

YWHAH
NM_003405.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.927

Publications

3 publications found

Variant links:

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]

YWHAH links:

ENSG00000285404 (HGNC:):

ENSG00000285404 links:

YWHAH-AS1 (HGNC:23051): (YWHAH antisense RNA 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

YWHAH-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YWHAH	NM_003405.4	MANE Select	c.-22G>T	5_prime_UTR	Exon 1 of 2	NP_003396.1	Q04917
YWHAH-AS1	NR_126507.1		n.130+521C>A	intron	N/A
YWHAH-AS1	NR_171018.1		n.134+521C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YWHAH	ENST00000248975.6	TSL:1 MANE Select	c.-22G>T	5_prime_UTR	Exon 1 of 2	ENSP00000248975.5	Q04917
ENSG00000285404	ENST00000646701.1		c.1787-11427G>T	intron	N/A	ENSP00000496158.1	A0A2R8YF50
YWHAH-AS1	ENST00000486651.1	TSL:1	n.286+521C>A	intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.16e-7

AC:

AN:

1225290

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

603250

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

24940

American (AMR)

AF:

0.00

AC:

AN:

23908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19768

East Asian (EAS)

AF:

0.00

AC:

AN:

24338

South Asian (SAS)

AF:

0.00

AC:

AN:

63502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3544

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

988566

Other (OTH)

AF:

0.00

AC:

AN:

48216

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.93

PromoterAI

0.0043

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over