2-55635975-CTA-C

Position:

• chr2-55635975-CTA-C

Variant summary

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

The NM_033109.5(PNPT1):​c.*260_*261del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 205,306 control chromosomes in the GnomAD database, including 10,070 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7135 hom., cov: 0)
  • Exomes 𝑓: 0.33 (2935 hom.)
• Consequence: PNPT1 NM_033109.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.446

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 2-55635975-CTA-C is Benign according to our data. Variant chr2-55635975-CTA-C is described in ClinVar as [Benign]. Clinvar id is 1246923.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	Protein	UniProt
PNPT1	NM_033109.5	c.*260_*261del		3_prime_UTR_variant	28/28	ENST00000447944.7	NP_149100.2
PNPT1	XM_005264629.3	c.*260_*261del		3_prime_UTR_variant	28/28		XP_005264686.1
PNPT1	XM_017005172.2	c.*260_*261del		3_prime_UTR_variant	27/27		XP_016860661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPT1	ENST00000447944.7	c.*260_*261del		3_prime_UTR_variant	28/28	1	NM_033109.5	ENSP00000400646	P1
PNPT1	ENST00000260604.8	c.*2154_*2155del		3_prime_UTR_variant, NMD_transcript_variant	27/27	5		ENSP00000260604
PNPT1	ENST00000415374.5	c.*260_*261del		3_prime_UTR_variant, NMD_transcript_variant	28/29	5		ENSP00000393953

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46239 AN: 151590 Hom.: 7135 Cov.: 0

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.325 AC: 17445 AN: 53598 Hom.: 2935 AF XY: 0.324 AC XY: 9073 AN XY: 27994

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.392

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.305 AC: 46254 AN: 151708 Hom.: 7135 Cov.: 0 AF XY: 0.306 AC XY: 22655 AN XY: 74108

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.288

Alfa AF: 0.179 Hom.: 187

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 26, 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: rs3069394; hg19: chr2-55863110;