3-3982382-T-C

Position:

• chr3-3982382-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

Genes affected

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

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPT1P1	ENST00000450418.1	n.1914A>G		non_coding_transcript_exon_variant	1/1
	ENST00000661097.1	n.131-20047T>C		intron_variant, non_coding_transcript_variant
SUMF1	ENST00000448413.5	c.1191+86187A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29870 AN: 152042 Hom.: 3383 Cov.: 33

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.: 25 AF XY: 0.188 AC XY: 123178 AN XY: 654538

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.0820

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.197 AC: 29902 AN: 152160 Hom.: 3387 Cov.: 33 AF XY: 0.196 AC XY: 14605 AN XY: 74384

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0722

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.204

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
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1353819; hg19: chr3-4024066;