NM_033109.5:c.-158G>C
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_033109.5(PNPT1):c.-158G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 847,598 control chromosomes in the GnomAD database, including 92,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.44 ( 15474 hom., cov: 33)
Exomes 𝑓: 0.46 ( 76979 hom. )
Consequence
PNPT1
NM_033109.5 upstream_gene
NM_033109.5 upstream_gene
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.814
Publications
10 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 13Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
- hearing loss disorderInheritance: AR Classification: DEFINITIVE Submitted by: G2P
- Leigh syndromeInheritance: AR Classification: MODERATE Submitted by: ClinGen
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- spinocerebellar ataxia type 25Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- autosomal recessive nonsyndromic hearing loss 70Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BP6
Variant 2-55693981-C-G is Benign according to our data. Variant chr2-55693981-C-G is described in CliVar as Benign. Clinvar id is 1241660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PNPT1 | NM_033109.5 | c.-158G>C | upstream_gene_variant | ENST00000447944.7 | NP_149100.2 | |||
PNPT1 | XM_005264629.3 | c.-394G>C | upstream_gene_variant | XP_005264686.1 | ||||
PNPT1 | XM_017005172.2 | c.-337G>C | upstream_gene_variant | XP_016860661.1 | ||||
PNPT1 | XM_047446161.1 | c.-158G>C | upstream_gene_variant | XP_047302117.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.438 AC: 66597AN: 151988Hom.: 15477 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
66597
AN:
151988
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.458 AC: 318835AN: 695492Hom.: 76979 AF XY: 0.452 AC XY: 159614AN XY: 353202 show subpopulations
GnomAD4 exome
AF:
AC:
318835
AN:
695492
Hom.:
AF XY:
AC XY:
159614
AN XY:
353202
show subpopulations
African (AFR)
AF:
AC:
5728
AN:
17602
American (AMR)
AF:
AC:
9168
AN:
19592
Ashkenazi Jewish (ASJ)
AF:
AC:
7303
AN:
15248
East Asian (EAS)
AF:
AC:
3880
AN:
32114
South Asian (SAS)
AF:
AC:
13833
AN:
51374
European-Finnish (FIN)
AF:
AC:
16737
AN:
30094
Middle Eastern (MID)
AF:
AC:
1030
AN:
2480
European-Non Finnish (NFE)
AF:
AC:
245737
AN:
492840
Other (OTH)
AF:
AC:
15419
AN:
34148
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
8266
16532
24797
33063
41329
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
4804
9608
14412
19216
24020
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.438 AC: 66615AN: 152106Hom.: 15474 Cov.: 33 AF XY: 0.436 AC XY: 32414AN XY: 74372 show subpopulations
GnomAD4 genome
AF:
AC:
66615
AN:
152106
Hom.:
Cov.:
33
AF XY:
AC XY:
32414
AN XY:
74372
show subpopulations
African (AFR)
AF:
AC:
13869
AN:
41472
American (AMR)
AF:
AC:
7467
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
AC:
1648
AN:
3468
East Asian (EAS)
AF:
AC:
568
AN:
5176
South Asian (SAS)
AF:
AC:
1245
AN:
4824
European-Finnish (FIN)
AF:
AC:
5987
AN:
10586
Middle Eastern (MID)
AF:
AC:
139
AN:
294
European-Non Finnish (NFE)
AF:
AC:
34444
AN:
67990
Other (OTH)
AF:
AC:
970
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1885
3770
5655
7540
9425
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
602
1204
1806
2408
3010
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
805
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Jun 23, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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