ENST00000539078.1:n.167+20G>C

Variant names:

• chr12-131929165-C-G
• rs12369083
• ENST00000539078.1:n.167+20G>C

Variant summary

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

The ENST00000539078.1(PUS1-AS1):​n.167+20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 150,912 control chromosomes in the GnomAD database, including 2,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2464 hom., cov: 26)
  • Exomes 𝑓: 0.0068 (0 hom.)
• Consequence: PUS1-AS1 ENST00000539078.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BP6: Variant 12-131929165-C-G is Benign according to our data. Variant chr12-131929165-C-G is described in ClinVar as [Benign]. Clinvar id is 676183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUS1	NM_025215.6	c.-558C>G		upstream_gene_variant		ENST00000376649.8	NP_079491.2
PUS1	NM_001002019.3	c.-250C>G		upstream_gene_variant			NP_001002019.1
PUS1	NM_001002020.3	c.-226C>G		upstream_gene_variant			NP_001002020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUS1	ENST00000376649.8	c.-558C>G		upstream_gene_variant		1	NM_025215.6	ENSP00000365837.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24718 AN: 150654 Hom.: 2461 Cov.: 26

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.112

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.00685 AC: 1 AN: 146 Hom.: 0 Cov.: 0 AF XY: 0.00980 AC XY: 1 AN XY: 102

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.164 AC: 24736 AN: 150766 Hom.: 2464 Cov.: 26 AF XY: 0.164 AC XY: 12103 AN XY: 73646

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.0977

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.160

Alfa AF: 0.0677 Hom.: 100

Bravo AF: 0.173

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-1.1
CADD	Benign	3.3
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12369083; hg19: chr12-132413710;