dbSNP rs1353819: PNPT1P1:n.1914A>G (chr3-3982382-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000450418.1(PNPT1P1):n.1914A>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 0.189 in 1,455,008 control chromosomes in the GnomAD database, including 32,104 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 0.20 ( 3387 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28717 hom. )

Consequence

PNPT1P1
ENST00000450418.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

2 publications found

Variant links:

Genes affected

PNPT1P1 (HGNC:44468): (polyribonucleotide nucleotidyltransferase 1 pseudogene 1)

PNPT1P1 links:

SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

SUMF1 Gene-Disease associations (from GenCC):

mucosulfatidosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P

SUMF1 links:

ENSG00000287720 (HGNC:):

ENSG00000287720 links:

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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=-0.62).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
PNPT1P1	ENST00000450418.1 link	n.1914A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
SUMF1	ENST00000448413.5 link	n.1191+86187A>G	intron_variant	Intron 9 of 12	2	ENSP00000404384.1	F5GXA0
ENSG00000287720	ENST00000661097.1 link	n.131-20047T>C	intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29870

AN:

152042

Hom.:

3383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.0722

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.206

GnomAD4 exome

AF:

0.188

AC:

245388

AN:

1302848

Hom.:

28717

Cov.:

AF XY:

0.188

AC XY:

123178

AN XY:

654538

show subpopulations

African (AFR)

AF:

0.252

AC:

7623

AN:

30268

American (AMR)

AF:

0.383

AC:

16893

AN:

44052

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

5048

AN:

24664

East Asian (EAS)

AF:

0.441

AC:

17149

AN:

38854

South Asian (SAS)

AF:

0.252

AC:

20962

AN:

83340

European-Finnish (FIN)

AF:

0.0820

AC:

4248

AN:

51820

Middle Eastern (MID)

AF:

0.184

AC:

718

AN:

3910

European-Non Finnish (NFE)

AF:

0.167

AC:

162147

AN:

971486

Other (OTH)

AF:

0.195

AC:

10600

AN:

54454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.587

Heterozygous variant carriers

8677

17353

26030

34706

43383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.197

AC:

29902

AN:

152160

Hom.:

3387

Cov.:

AF XY:

0.196

AC XY:

14605

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.235

AC:

9767

AN:

41490

American (AMR)

AF:

0.298

AC:

4559

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

625

AN:

3472

East Asian (EAS)

AF:

0.403

AC:

2079

AN:

5156

South Asian (SAS)

AF:

0.240

AC:

1155

AN:

4820

European-Finnish (FIN)

AF:

0.0722

AC:

767

AN:

10618

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10301

AN:

68006

Other (OTH)

AF:

0.204

AC:

432

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1185

2369

3554

4738

5923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.174

Hom.:

303

Bravo

AF:

0.217

Asia WGS

AF:

0.302

AC:

1050

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.27

(source)

DANN

Benign

0.58

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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rs1353819

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