rs2586954

Positions:

• chr2-55665126-A-C

Variant summary

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

The NM_033109.5(PNPT1):​c.1176+1865T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,934 control chromosomes in the GnomAD database, including 16,320 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 (16320 hom., cov: 32)
• Consequence: PNPT1 NM_033109.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPT1	NM_033109.5	c.1176+1865T>G		intron_variant		ENST00000447944.7	NP_149100.2
PNPT1	XM_005264629.3	c.936+1865T>G		intron_variant			XP_005264686.1
PNPT1	XM_017005172.2	c.936+1865T>G		intron_variant			XP_016860661.1
PNPT1	XM_047446161.1	c.1176+1865T>G		intron_variant			XP_047302117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPT1	ENST00000447944.7	c.1176+1865T>G		intron_variant		1	NM_033109.5	ENSP00000400646	P1
PNPT1	ENST00000260604.8	c.*731+1865T>G		intron_variant, NMD_transcript_variant		5		ENSP00000260604
PNPT1	ENST00000415374.5	c.1176+1865T>G		intron_variant, NMD_transcript_variant		5		ENSP00000393953
PNPT1	ENST00000415489.1	c.250+1865T>G		intron_variant, NMD_transcript_variant		3		ENSP00000411057

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68292 AN: 151818 Hom.: 16325 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.450 AC: 68302 AN: 151934 Hom.: 16320 Cov.: 32 AF XY: 0.448 AC XY: 33255 AN XY: 74260

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.473

Alfa AF: 0.492 Hom.: 8753

Bravo AF: 0.438

Asia WGS AF: 0.251 AC: 871 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.83
DANN	Benign	0.44

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: rs2586954; hg19: chr2-55892261;