Genetic Variant PUS1-AS1:n.31T>G (chr12-131929053-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000828047.1(PUS1-AS1):n.31T>G variant causes a non coding transcript exon 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
ENST00000828047.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.666

Publications

2 publications found

Variant links:

Genes affected

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

PUS1-AS1 links:

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]

PUS1 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
myopathy, lactic acidosis, and sideroblastic anemia 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
myopathy, lactic acidosis, and sideroblastic anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PUS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000828047.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PUS1	NM_025215.6	MANE Select	c.-670A>C	upstream_gene	N/A	NP_079491.2	E5KMT5
PUS1	NM_001002019.3		c.-362A>C	upstream_gene	N/A	NP_001002019.1	E5KMT6
PUS1	NM_001002020.3		c.-338A>C	upstream_gene	N/A	NP_001002020.1	E5KMT6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
PUS1-AS1	ENST00000828047.1		n.31T>G	non_coding_transcript_exon	Exon 1 of 3
PUS1-AS1	ENST00000828048.1		n.1T>G	non_coding_transcript_exon	Exon 1 of 3
PUS1-AS1	ENST00000539078.2	TSL:5	n.462+132T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23180

AN:

151656

Hom.:

2306

Cov.:

show subpopulations

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:

AN:

122

Hom.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0889

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.153

AC:

23174

AN:

151766

Hom.:

2305

Cov.:

AF XY:

0.154

AC XY:

11385

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.0760

AC:

3153

AN:

41486

American (AMR)

AF:

0.183

AC:

2794

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

662

AN:

3464

East Asian (EAS)

AF:

0.527

AC:

2639

AN:

5008

South Asian (SAS)

AF:

0.101

AC:

487

AN:

4822

European-Finnish (FIN)

AF:

0.155

AC:

1636

AN:

10560

Middle Eastern (MID)

AF:

0.117

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.166

AC:

11292

AN:

67854

Other (OTH)

AF:

0.152

AC:

321

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

875

1750

2625

3500

4375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0625

Hom.:

105

Bravo

AF:

0.159

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.2

CADD

Benign

7.3

(source)

DANN

Benign

0.21

PhyloP100

-0.67

PromoterAI

-0.076

Neutral

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over