Genetic Variant NM_005443.5:c.*70G>A (chr4-107614179-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005443.5(PAPSS1):c.*70G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,462,762 control chromosomes in the GnomAD database, including 41,374 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3264 hom., cov: 32)

Exomes 𝑓: 0.24 ( 38110 hom. )

Consequence

PAPSS1
NM_005443.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0580

Publications

13 publications found

Variant links:

Genes affected

PAPSS1 (HGNC:8603): (3'-phosphoadenosine 5'-phosphosulfate synthase 1) Three-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS) is the sulfate donor cosubstrate for all sulfotransferase (SULT) enzymes (Xu et al., 2000 [PubMed 10679223]). SULTs catalyze the sulfate conjugation of many endogenous and exogenous compounds, including drugs and other xenobiotics. In humans, PAPS is synthesized from adenosine 5-prime triphosphate (ATP) and inorganic sulfate by 2 isoforms, PAPSS1 and PAPSS2 (MIM 603005).[supplied by OMIM, Mar 2008]

PAPSS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PAPSS1	NM_005443.5 link	c.*70G>A	3_prime_UTR_variant	Exon 12 of 12	ENST00000265174.5	NP_005434.4	O43252
PAPSS1	XM_011532400.3 link	c.*70G>A	3_prime_UTR_variant	Exon 12 of 12		XP_011530702.1	O43252
PAPSS1	XM_011532401.2 link	c.*70G>A	3_prime_UTR_variant	Exon 12 of 12		XP_011530703.1	O43252

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000265174.5 link	c.*70G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_005443.5	ENSP00000265174.4		O43252
PAPSS1	ENST00000514815.1 link	n.174+17452G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29030

AN:

151832

Hom.:

3257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0689

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.210

GnomAD4 exome

AF:

0.235

AC:

308543

AN:

1310812

Hom.:

38110

Cov.:

AF XY:

0.233

AC XY:

151788

AN XY:

651424

show subpopulations

African (AFR)

AF:

0.0593

AC:

1727

AN:

29142

American (AMR)

AF:

0.294

AC:

9930

AN:

33764

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

4594

AN:

23014

East Asian (EAS)

AF:

0.384

AC:

14513

AN:

37828

South Asian (SAS)

AF:

0.150

AC:

11277

AN:

74970

European-Finnish (FIN)

AF:

0.255

AC:

13277

AN:

52054

Middle Eastern (MID)

AF:

0.166

AC:

883

AN:

5312

European-Non Finnish (NFE)

AF:

0.240

AC:

240415

AN:

1000150

Other (OTH)

AF:

0.219

AC:

11927

AN:

54578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

10994

21989

32983

43978

54972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8212

16424

24636

32848

41060

<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:

0.191

AC:

29047

AN:

151950

Hom.:

3264

Cov.:

AF XY:

0.192

AC XY:

14290

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.0689

AC:

2859

AN:

41498

American (AMR)

AF:

0.239

AC:

3647

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

716

AN:

3468

East Asian (EAS)

AF:

0.365

AC:

1876

AN:

5146

South Asian (SAS)

AF:

0.148

AC:

709

AN:

4802

European-Finnish (FIN)

AF:

0.257

AC:

2707

AN:

10536

Middle Eastern (MID)

AF:

0.199

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.231

AC:

15724

AN:

67932

Other (OTH)

AF:

0.214

AC:

449

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1139

2279

3418

4558

5697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.220

Hom.:

12206

Bravo

AF:

0.193

Asia WGS

AF:

0.210

AC:

731

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.2

(source)

DANN

Benign

0.80

PhyloP100

0.058

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over