Variant 2-55636078-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.138

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00295 (449/152286) while in subpopulation NFE AF= 0.00384 (261/68018). AF 95% confidence interval is 0.00345. There are 6 homozygotes in gnomad4. There are 242 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
PNPT1	NM_033109.5 link	c.*159T>A	3_prime_UTR_variant	28/28	ENST00000447944.7	NP_149100.2	Q8TCS8
PNPT1	XM_005264629.3 link	c.*159T>A	3_prime_UTR_variant	28/28		XP_005264686.1
PNPT1	XM_017005172.2 link	c.*159T>A	3_prime_UTR_variant	27/27		XP_016860661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPT1	ENST00000447944 link	c.*159T>A		3_prime_UTR_variant	28/28	1	NM_033109.5	ENSP00000400646.2		Q8TCS8

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

449

AN:

152168

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00380

AC XY:

503

AN XY:

132472

show subpopulations

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.:

Cov.:

AF XY:

0.00325

AC XY:

242

AN XY:

74472

show subpopulations

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.:

Bravo

AF:

0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over