ENST00000450418.1:n.2112T>C

Variant names:

• chr3-3982184-A-G
• rs1385467
• ENST00000450418.1:n.2112T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 5 publications found

Genes affected

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

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

ENSG00000287720 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000450418.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPT1P1	ENST00000450418.1	TSL:6	n.2112T>C		non_coding_transcript_exon	Exon 1 of 1
	SUMF1	ENST00000448413.5	TSL:2	n.1191+86385T>C		intron	N/A	ENSP00000404384.1
	ENSG00000287720	ENST00000661097.1		n.131-20245A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58970 AN: 151974 Hom.: 14368 Cov.: 33

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.: 6 AF XY: 0.333 AC XY: 102064 AN XY: 306776

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

GnomAD4 genome AF: 0.388 AC: 59076 AN: 152092 Hom.: 14411 Cov.: 33 AF XY: 0.391 AC XY: 29076 AN XY: 74336

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: 78 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16053 AN: 67978

Other (OTH) AF: 0.375 AC: 793 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.67
DANN	Benign	0.43
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1385467; hg19: chr3-4023868;