rs782652

Positions:

• chr2-55635640-C-A
• chr2-55635640-C-T

Variant summary

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

The NM_033109.5(PNPT1):​c.*597G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,222 control chromosomes in the GnomAD database, including 16,218 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 0.45 (16218 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PNPT1 NM_033109.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

Genes affected

PNPT1 (HGNC:23166): (polyribonucleotide nucleotidyltransferase 1) The protein encoded by this gene belongs to the evolutionary conserved polynucleotide phosphorylase family comprised of phosphate dependent 3'-to-5' exoribonucleases implicated in RNA processing and degradation. This enzyme is predominantly localized in the mitochondrial intermembrane space and is involved in import of RNA to mitochondria. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency-13 and autosomal recessive nonsyndromic deafness-70. Related pseudogenes are found on chromosomes 3 and 7. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPT1	NM_033109.5	c.*597G>T		3_prime_UTR_variant	28/28	ENST00000447944.7	NP_149100.2
PNPT1	XM_005264629.3	c.*597G>T		3_prime_UTR_variant	28/28		XP_005264686.1
PNPT1	XM_017005172.2	c.*597G>T		3_prime_UTR_variant	27/27		XP_016860661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPT1	ENST00000447944	c.*597G>T		3_prime_UTR_variant	28/28	1	NM_033109.5	ENSP00000400646.2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68008 AN: 151104 Hom.: 16224 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.471

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.450 AC: 68018 AN: 151222 Hom.: 16218 Cov.: 32 AF XY: 0.448 AC XY: 33102 AN XY: 73840

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.468

Alfa AF: 0.458 Hom.: 4191

Bravo AF: 0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs782652; hg19: chr2-55862775;