12-131929174-C-T

Position:

• chr12-131929174-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The variant allele was found at a frequency of 0.533 in 148,702 control chromosomes in the GnomAD database, including 24,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (24584 hom., cov: 25)
  • Exomes 𝑓: 0.65 (24 hom.)
• Consequence: intergenic_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0740

Genes affected

(HGNC:):

PUS1 (HGNC:15508): (pseudouridine synthase 1) This gene encodes a pseudouridine synthase that converts uridine to pseudouridine once it has been incorporated into an RNA molecule. The encoded enzyme may play an essential role in tRNA function and in stabilizing the secondary and tertiary structure of many RNAs. A mutation in this gene has been linked to mitochondrial myopathy and sideroblastic anemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.18).
• BP6: Variant 12-131929174-C-T is Benign according to our data. Variant chr12-131929174-C-T is described in ClinVar as [Benign]. Clinvar id is 1247005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.131929174C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUS1-AS1	ENST00000539078.1	n.167+11G>A		intron_variant		5
PUS1	ENST00000443358.6	c.-217C>T		upstream_gene_variant		1		ENSP00000392451.2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 79152 AN: 148512 Hom.: 24587 Cov.: 25

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.711

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.564

GnomAD4 exome AF: 0.651 AC: 69 AN: 106 Hom.: 24 Cov.: 0 AF XY: 0.724 AC XY: 55 AN XY: 76

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.650

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.909

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.533 AC: 79147 AN: 148596 Hom.: 24584 Cov.: 25 AF XY: 0.530 AC XY: 38438 AN XY: 72460

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.565

Alfa AF: 0.659 Hom.: 29335

Bravo AF: 0.508

Asia WGS AF: 0.471 AC: 1634 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	3.2
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12307678; hg19: chr12-132413719;