rs3069394

Variant names:

• chr2-55635975-CTA-C
• rs3069394
• NM_033109.5:c.*260_*261delTA

Your query was ambiguous. Multiple possible variants found:

• chr2-55635975-CTA-C
• chr2-55635975-CTA-CTATA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_033109.5(PNPT1):​c.*260_*261delTA 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
• Publications: 2 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 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hearing loss disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spinocerebellar ataxia type 25

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• autosomal recessive nonsyndromic hearing loss 70

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033109.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPT1	NM_033109.5	MANE Select	c.*260_*261delTA		3_prime_UTR	Exon 28 of 28	NP_149100.2	Q8TCS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPT1	ENST00000447944.7	TSL:1 MANE Select	c.*260_*261delTA		3_prime_UTR	Exon 28 of 28	ENSP00000400646.2	Q8TCS8
	PNPT1	ENST00000867135.1		c.*260_*261delTA		3_prime_UTR	Exon 28 of 28	ENSP00000537194.1
	PNPT1	ENST00000917023.1		c.*260_*261delTA		3_prime_UTR	Exon 28 of 28	ENSP00000587082.1

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

African (AFR) AF: 0.250 AC: 499 AN: 1996

American (AMR) AF: 0.378 AC: 844 AN: 2230

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 648 AN: 2124

East Asian (EAS) AF: 0.392 AC: 1615 AN: 4116

South Asian (SAS) AF: 0.430 AC: 479 AN: 1114

European-Finnish (FIN) AF: 0.341 AC: 585 AN: 1718

Middle Eastern (MID) AF: 0.286 AC: 72 AN: 252

European-Non Finnish (NFE) AF: 0.318 AC: 11603 AN: 36486

Other (OTH) AF: 0.309 AC: 1100 AN: 3562

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

African (AFR) AF: 0.255 AC: 10522 AN: 41322

American (AMR) AF: 0.336 AC: 5133 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1098 AN: 3466

East Asian (EAS) AF: 0.344 AC: 1774 AN: 5164

South Asian (SAS) AF: 0.391 AC: 1884 AN: 4818

European-Finnish (FIN) AF: 0.299 AC: 3138 AN: 10478

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21624 AN: 67896

Other (OTH) AF: 0.288 AC: 607 AN: 2110

Alfa AF: 0.179 Hom.: 187

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3069394; hg19: chr2-55863110; COSMIC: COSV53180206; COSMIC: COSV53180206;