rs782606

Positions:

• chr2-55659467-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033109.5(PNPT1):​c.1284+690A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,628 control chromosomes in the GnomAD database, including 16,170 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16170 hom., cov: 30)
• Consequence: PNPT1 NM_033109.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPT1	NM_033109.5	c.1284+690A>G		intron_variant		ENST00000447944.7
PNPT1	XM_005264629.3	c.1044+690A>G		intron_variant
PNPT1	XM_017005172.2	c.1044+690A>G		intron_variant
PNPT1	XM_047446161.1	c.1284+690A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPT1	ENST00000447944.7	c.1284+690A>G		intron_variant		1	NM_033109.5	P1
PNPT1	ENST00000260604.8	c.*839+690A>G		intron_variant, NMD_transcript_variant		5
PNPT1	ENST00000415374.5	c.1284+690A>G		intron_variant, NMD_transcript_variant		5
PNPT1	ENST00000415489.1	c.358+690A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67784 AN: 151512 Hom.: 16175 Cov.: 30

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.474

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.447 AC: 67797 AN: 151628 Hom.: 16170 Cov.: 30 AF XY: 0.445 AC XY: 32952 AN XY: 74046

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.471

Alfa AF: 0.511 Hom.: 26094

Bravo AF: 0.435

Asia WGS AF: 0.233 AC: 810 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.35

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: rs782606; hg19: chr2-55886602;