Genetic Variant PNPT1P1:n.2112T>C (chr3-3982184-A-G) – 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.2112T>C 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 0.341 in 711,242 control chromosomes in the GnomAD database, including 52,801 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 0.39 ( 14411 hom., cov: 33)

Exomes 𝑓: 0.33 ( 38390 hom. )

Consequence

PNPT1P1
ENST00000450418.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.269

Publications

5 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=-0.73).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 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
PNPT1P1	ENST00000450418.1 link	n.2112T>C	non_coding_transcript_exon_variant	Exon 1 of 1	6
SUMF1	ENST00000448413.5 link	n.1191+86385T>C	intron_variant	Intron 9 of 12	2	ENSP00000404384.1
ENSG00000287720	ENST00000661097.1 link	n.131-20245A>G	intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58970

AN:

151974

Hom.:

14368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.367

GnomAD4 exome

AF:

0.328

AC:

183395

AN:

559150

Hom.:

38390

Cov.:

AF XY:

0.333

AC XY:

102064

AN XY:

306776

show subpopulations

African (AFR)

AF:

0.625

AC:

9735

AN:

15580

American (AMR)

AF:

0.491

AC:

20186

AN:

41082

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

5022

AN:

18180

East Asian (EAS)

AF:

0.799

AC:

23383

AN:

29264

South Asian (SAS)

AF:

0.511

AC:

35382

AN:

69304

European-Finnish (FIN)

AF:

0.174

AC:

7776

AN:

44608

Middle Eastern (MID)

AF:

0.305

AC:

1100

AN:

3604

European-Non Finnish (NFE)

AF:

0.232

AC:

71794

AN:

309470

Other (OTH)

AF:

0.321

AC:

9017

AN:

28058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

5974

11948

17922

23896

29870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

968

1936

2904

3872

4840

<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:

0.388

AC:

59076

AN:

152092

Hom.:

14411

Cov.:

AF XY:

0.391

AC XY:

29076

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.632

AC:

26216

AN:

41474

American (AMR)

AF:

0.414

AC:

6317

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

939

AN:

3472

East Asian (EAS)

AF:

0.774

AC:

4001

AN:

5170

South Asian (SAS)

AF:

0.534

AC:

2570

AN:

4814

European-Finnish (FIN)

AF:

0.175

AC:

1848

AN:

10590

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16053

AN:

67978

Other (OTH)

AF:

0.375

AC:

793

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1590

3181

4771

6362

7952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.295

Hom.:

3017

Bravo

AF:

0.414

Asia WGS

AF:

0.651

AC:

2260

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.67

(source)

DANN

Benign

0.43

PhyloP100

-0.27

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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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