2-55636225-T-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_033109.5(PNPT1):c.*11_*12insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18319 hom., cov: 0)
  • Exomes 𝑓: 0.45 (56036 hom.)
  • Failed GnomAD Quality Control
• Consequence: PNPT1 NM_033109.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.870

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 -16 ACMG points.

• BP6: Variant 2-55636225-T-TA is Benign according to our data. Variant chr2-55636225-T-TA is described in ClinVar as [Benign]. Clinvar id is 215003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPT1	NM_033109.5	c.*11_*12insT		3_prime_UTR_variant	28/28	ENST00000447944.7
PNPT1	XM_005264629.3	c.*11_*12insT		3_prime_UTR_variant	28/28
PNPT1	XM_017005172.2	c.*11_*12insT		3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPT1	ENST00000447944.7	c.*11_*12insT		3_prime_UTR_variant	28/28	1	NM_033109.5	P1
PNPT1	ENST00000260604.8	c.*1905_*1906insT		3_prime_UTR_variant, NMD_transcript_variant	27/27	5
PNPT1	ENST00000415374.5	c.*11_*12insT		3_prime_UTR_variant, NMD_transcript_variant	28/29	5

Frequencies

GnomAD3 genomes AF: 0.482 AC: 72111 AN: 149726 Hom.: 18323 Cov.: 0

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.533

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.518

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.452 AC: 538298 AN: 1190444 Hom.: 56036 Cov.: 30 AF XY: 0.450 AC XY: 266012 AN XY: 591094

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.396

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.440

GnomAD4 genome AF: 0.481 AC: 72119 AN: 149814 Hom.: 18319 Cov.: 0 AF XY: 0.481 AC XY: 35142 AN XY: 73074

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.514

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined oxidative phosphorylation defect type 13 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2014

The variant is found in MITONUC-MITOP panel(s). -

Autosomal recessive nonsyndromic hearing loss 70 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs35916020; hg19: chr2-55863360;