chr2-55693981-C-G

Variant names:

• chr2-55693981-C-G
• rs782584
• NM_033109.5:c.-158G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.814

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 -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 ClinVar 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

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPT1	ENST00000447944.7	c.-158G>C		upstream_gene_variant		1	NM_033109.5	ENSP00000400646.2

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66597 AN: 151988 Hom.: 15477 Cov.: 33

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.458 AC: 318835 AN: 695492 Hom.: 76979 AF XY: 0.452 AC XY: 159614 AN XY: 353202

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.556

Gnomad4 NFE exome AF: 0.499

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome AF: 0.438 AC: 66615 AN: 152106 Hom.: 15474 Cov.: 33 AF XY: 0.436 AC XY: 32414 AN XY: 74372

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.459

Alfa AF: 0.474 Hom.: 2144

Bravo AF: 0.428

Asia WGS AF: 0.231 AC: 805 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs782584; hg19: chr2-55921116;