2-55636078-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033109.5(PNPT1):c.*159T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 412,252 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (5 hom.)
• Consequence: PNPT1 NM_033109.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.138

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-55636078-A-T is Benign according to our data. Variant chr2-55636078-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1201859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPT1	NM_033109.5	c.*159T>A		3_prime_UTR_variant	28/28	ENST00000447944.7
PNPT1	XM_005264629.3	c.*159T>A		3_prime_UTR_variant	28/28
PNPT1	XM_017005172.2	c.*159T>A		3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPT1	ENST00000447944.7	c.*159T>A		3_prime_UTR_variant	28/28	1	NM_033109.5	P1
PNPT1	ENST00000260604.8	c.*2053T>A		3_prime_UTR_variant, NMD_transcript_variant	27/27	5
PNPT1	ENST00000415374.5	c.*159T>A		3_prime_UTR_variant, NMD_transcript_variant	28/29	5

Frequencies

GnomAD3 genomes AF: 0.00295 AC: 449 AN: 152168 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00384

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00382 AC: 992 AN: 259966 Hom.: 5 Cov.: 4 AF XY: 0.00380 AC XY: 503 AN XY: 132472

Gnomad4 AFR exome AF: 0.000959

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.000815

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00249

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.00406

Gnomad4 OTH exome AF: 0.00325

GnomAD4 genome AF: 0.00295 AC: 449 AN: 152286 Hom.: 6 Cov.: 33 AF XY: 0.00325 AC XY: 242 AN XY: 74472

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.00384

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00386 Hom.: 0

Bravo AF: 0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.17
Dann	Benign	0.17

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: rs568249156; hg19: chr2-55863213;