rs782652

Variant names:

• chr2-55635640-C-A
• rs782652
• NM_033109.5:c.*597G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

PNPT1 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hearing loss disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spinocerebellar ataxia type 25

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• autosomal recessive nonsyndromic hearing loss 70

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PNPT1	NM_033109.5	c.*597G>T		3_prime_UTR_variant	Exon 28 of 28	ENST00000447944.7	NP_149100.2
PNPT1	XM_005264629.3	c.*597G>T		3_prime_UTR_variant	Exon 28 of 28		XP_005264686.1
PNPT1	XM_017005172.2	c.*597G>T		3_prime_UTR_variant	Exon 27 of 27		XP_016860661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPT1	ENST00000447944.7	c.*597G>T		3_prime_UTR_variant	Exon 28 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.330 AC: 13606 AN: 41258

American (AMR) AF: 0.500 AC: 7539 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1620 AN: 3466

East Asian (EAS) AF: 0.112 AC: 576 AN: 5124

South Asian (SAS) AF: 0.272 AC: 1285 AN: 4716

European-Finnish (FIN) AF: 0.595 AC: 6216 AN: 10440

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35778 AN: 67836

Other (OTH) AF: 0.468 AC: 982 AN: 2098

Alfa AF: 0.459 Hom.: 4708

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
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs782652; hg19: chr2-55862775;