2-55635931-TTCTA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_033109.5(PNPT1):c.*302_*305del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 167,482 control chromosomes in the GnomAD database, including 8,179 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7247 hom., cov: 0)
  • Exomes 𝑓: 0.34 (932 hom.)
• Consequence: PNPT1 NM_033109.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.03

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 -10 ACMG points.

• BP6: Variant 2-55635931-TTCTA-T is Benign according to our data. Variant chr2-55635931-TTCTA-T is described in ClinVar as [Benign]. Clinvar id is 1251542.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPT1	NM_033109.5	c.*302_*305del		3_prime_UTR_variant	28/28	ENST00000447944.7
PNPT1	XM_005264629.3	c.*302_*305del		3_prime_UTR_variant	28/28
PNPT1	XM_017005172.2	c.*302_*305del		3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPT1	ENST00000447944.7	c.*302_*305del		3_prime_UTR_variant	28/28	1	NM_033109.5	P1
PNPT1	ENST00000260604.8	c.*2196_*2199del		3_prime_UTR_variant, NMD_transcript_variant	27/27	5
PNPT1	ENST00000415374.5	c.*302_*305del		3_prime_UTR_variant, NMD_transcript_variant	28/29	5

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46593 AN: 151670 Hom.: 7246 Cov.: 0

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.344 AC: 5398 AN: 15696 Hom.: 932 AF XY: 0.341 AC XY: 2909 AN XY: 8542

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.340

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.307 AC: 46612 AN: 151786 Hom.: 7247 Cov.: 0 AF XY: 0.308 AC XY: 22831 AN XY: 74174

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.289

Alfa AF: 0.313 Hom.: 886

Bravo AF: 0.309

Asia WGS AF: 0.336 AC: 1166 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3838524; hg19: chr2-55863066;