dbSNP rs1215451501: PUS1:c.-80G>A (chr12-131929643-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025215.6(PUS1):c.-80G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,252,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PUS1
NM_025215.6 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.832

Publications

0 publications found

Variant links:

Genes affected

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 links:

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

PUS1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025215.6. 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.-80G>A	5_prime_UTR	Exon 1 of 6	NP_079491.2	E5KMT5
PUS1	NM_001002019.3		c.-11+239G>A	intron	N/A	NP_001002019.1	E5KMT6
PUS1	NM_001002020.3		c.-11+263G>A	intron	N/A	NP_001002020.1	E5KMT6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PUS1	ENST00000376649.8	TSL:1 MANE Select	c.-80G>A	5_prime_UTR	Exon 1 of 6	ENSP00000365837.3	Q9Y606-1
PUS1	ENST00000443358.6	TSL:1	c.-11+263G>A	intron	N/A	ENSP00000392451.2	Q9Y606-2
PUS1	ENST00000890860.1		c.-80G>A	5_prime_UTR	Exon 1 of 6	ENSP00000560919.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000273

AC:

AN:

1100226

Hom.:

Cov.:

AF XY:

0.0000329

AC XY:

AN XY:

547098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24164

American (AMR)

AF:

0.0000365

AC:

AN:

27402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19260

East Asian (EAS)

AF:

0.00

AC:

AN:

30620

South Asian (SAS)

AF:

0.00

AC:

AN:

63692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3482

European-Non Finnish (NFE)

AF:

0.0000341

AC:

AN:

851352

Other (OTH)

AF:

0.00

AC:

AN:

47518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Myopathy, lactic acidosis, and sideroblastic anemia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.83

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over