2-55636238-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_033109.5(PNPT1):​c.2351G>T​(p.Ter784Leuext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PNPT1
NM_033109.5 stop_lost

Scores

2
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_033109.5 Downstream stopcodon found after 51 codons.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PNPT1NM_033109.5 linkc.2351G>T p.Ter784Leuext*? stop_lost 28/28 ENST00000447944.7 NP_149100.2 Q8TCS8
PNPT1XM_005264629.3 linkc.2111G>T p.Ter704Leuext*? stop_lost 28/28 XP_005264686.1
PNPT1XM_017005172.2 linkc.2111G>T p.Ter704Leuext*? stop_lost 27/27 XP_016860661.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PNPT1ENST00000447944.7 linkc.2351G>T p.Ter784Leuext*? stop_lost 28/281 NM_033109.5 ENSP00000400646.2 Q8TCS8
PNPT1ENST00000260604.8 linkn.*1893G>T non_coding_transcript_exon_variant 27/275 ENSP00000260604.4 H7BXF6
PNPT1ENST00000415374.5 linkn.2351G>T non_coding_transcript_exon_variant 28/295 ENSP00000393953.1 Q8TCS8
PNPT1ENST00000260604.8 linkn.*1893G>T 3_prime_UTR_variant 27/275 ENSP00000260604.4 H7BXF6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1423186
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
707178
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxDec 08, 2023Stop codon loss and change to a Leu codon, leading to protein extension and the addition of 14 amino acids at the C-terminus; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
15
DANN
Benign
0.55
Eigen
Uncertain
0.36
Eigen_PC
Benign
0.076
FATHMM_MKL
Uncertain
0.94
D
Vest4
0.0060
GERP RS
3.1

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.

Other links and lift over

dbSNP: rs1256655826; hg19: chr2-55863373; API