rs10495571

chr2-9595937-A-G

Variant summary

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

The NM_006826.4(YWHAQ):c.295-4422T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,034 control chromosomes in the GnomAD database, including 2,172 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 0.15 (2172 hom., cov: 31)
• Consequence: YWHAQ NM_006826.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAQ	NM_006826.4	c.295-4422T>C		intron_variant		ENST00000238081.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAQ	ENST00000238081.8	c.295-4422T>C		intron_variant		1	NM_006826.4	P1
YWHAQ	ENST00000381844.8	c.295-4422T>C		intron_variant		1		P1
YWHAQ	ENST00000446619.1	c.295-4422T>C		intron_variant		3
YWHAQ	ENST00000474715.1	n.61-4422T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23027 AN: 151916 Hom.: 2174 Cov.: 31

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.151 AC: 23025 AN: 152034 Hom.: 2172 Cov.: 31 AF XY: 0.150 AC XY: 11175 AN XY: 74310

Gnomad4 AFR AF: 0.0714

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.00445

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.162

Alfa AF: 0.192 Hom.: 4046

Bravo AF: 0.141

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.62
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: rs10495571; hg19: chr2-9736066;