Variant chr2-55636225-T-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.870

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	#exon/exons	MANE	Protein
PNPT1	NM_033109.5 linkuse as main transcript	c.11_12insT	3_prime_UTR_variant	28/28	ENST00000447944.7	NP_149100.2
PNPT1	XM_005264629.3 linkuse as main transcript	c.11_12insT	3_prime_UTR_variant	28/28		XP_005264686.1
PNPT1	XM_017005172.2 linkuse as main transcript	c.11_12insT	3_prime_UTR_variant	27/27		XP_016860661.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
PNPT1	ENST00000447944.7 linkuse as main transcript	c.11_12insT	3_prime_UTR_variant	28/28	1	NM_033109.5	ENSP00000400646	P1
PNPT1	ENST00000260604.8 linkuse as main transcript	c.1905_1906insT	3_prime_UTR_variant, NMD_transcript_variant	27/27	5		ENSP00000260604
PNPT1	ENST00000415374.5 linkuse as main transcript	c.11_12insT	3_prime_UTR_variant, NMD_transcript_variant	28/29	5		ENSP00000393953

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

72111

AN:

149726

Hom.:

18323

Cov.:

show subpopulations

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.:

AF XY:

0.450

AC XY:

266012

AN XY:

591094

show subpopulations

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.:

AF XY:

0.481

AC XY:

35142

AN XY:

73074

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2014

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

Combined oxidative phosphorylation defect type 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

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

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over