12-131929053-A-C

Variant names:

• chr12-131929053-A-C
• rs78255464
• ENST00000539078.1:n.167+132T>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000539078.1(PUS1-AS1):​n.167+132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,888 control chromosomes in the GnomAD database, including 2,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2305 hom., cov: 31)
  • Exomes 𝑓: 0.082 (0 hom.)
• Consequence: PUS1-AS1 ENST00000539078.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.666

Genes affected

PUS1-AS1 (HGNC:40706): (PUS1 antisense RNA 1)

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.2).
• BP6: Variant 12-131929053-A-C is Benign according to our data. Variant chr12-131929053-A-C is described in ClinVar as [Benign]. Clinvar id is 676197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUS1	NM_025215.6	c.-670A>C		upstream_gene_variant		ENST00000376649.8	NP_079491.2
PUS1	NM_001002019.3	c.-362A>C		upstream_gene_variant			NP_001002019.1
PUS1	NM_001002020.3	c.-338A>C		upstream_gene_variant			NP_001002020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUS1	ENST00000376649.8	c.-670A>C		upstream_gene_variant		1	NM_025215.6	ENSP00000365837.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23180 AN: 151656 Hom.: 2306 Cov.: 31

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.0820 AC: 10 AN: 122 Hom.: 0 AF XY: 0.100 AC XY: 9 AN XY: 90

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.0889

GnomAD4 genome AF: 0.153 AC: 23174 AN: 151766 Hom.: 2305 Cov.: 31 AF XY: 0.154 AC XY: 11385 AN XY: 74162

Gnomad4 AFR AF: 0.0760

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.152

Alfa AF: 0.0625 Hom.: 105

Bravo AF: 0.159

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	7.3
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs78255464; hg19: chr12-132413598;