chr2-55667112-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_033109.5(PNPT1):c.1074-19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,570,290 control chromosomes in the GnomAD database, including 189,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.44 ( 15891 hom., cov: 32)
Exomes 𝑓: 0.49 ( 173284 hom. )
Consequence
PNPT1
NM_033109.5 intron
NM_033109.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.247
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 2-55667112-T-C is Benign according to our data. Variant chr2-55667112-T-C is described in ClinVar as [Benign]. Clinvar id is 138735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-55667112-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPT1 | NM_033109.5 | c.1074-19A>G | intron_variant | ENST00000447944.7 | |||
PNPT1 | XM_005264629.3 | c.834-19A>G | intron_variant | ||||
PNPT1 | XM_017005172.2 | c.834-19A>G | intron_variant | ||||
PNPT1 | XM_047446161.1 | c.1074-19A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPT1 | ENST00000447944.7 | c.1074-19A>G | intron_variant | 1 | NM_033109.5 | P1 | |||
PNPT1 | ENST00000260604.8 | c.*629-19A>G | intron_variant, NMD_transcript_variant | 5 | |||||
PNPT1 | ENST00000415374.5 | c.1074-19A>G | intron_variant, NMD_transcript_variant | 5 | |||||
PNPT1 | ENST00000415489.1 | c.148-19A>G | intron_variant, NMD_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.444 AC: 67525AN: 151930Hom.: 15896 Cov.: 32
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GnomAD3 exomes AF: 0.440 AC: 108601AN: 246766Hom.: 25934 AF XY: 0.438 AC XY: 58457AN XY: 133474
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GnomAD4 exome AF: 0.486 AC: 689819AN: 1418242Hom.: 173284 Cov.: 24 AF XY: 0.481 AC XY: 340393AN XY: 708056
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GnomAD4 genome ? AF: 0.444 AC: 67539AN: 152048Hom.: 15891 Cov.: 32 AF XY: 0.442 AC XY: 32870AN XY: 74336
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 05, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 21, 2015 | - - |
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 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at