chr2-55636166-A-G

Position:

• chr2-55636166-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000447944.7(PNPT1):​c.*71T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,108,716 control chromosomes in the GnomAD database, including 240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (149 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (91 hom.)
• Consequence: PNPT1 ENST00000447944.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.560

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-55636166-A-G is Benign according to our data. Variant chr2-55636166-A-G is described in ClinVar as [Benign]. Clinvar id is 1261362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPT1	NM_033109.5	c.*71T>C		3_prime_UTR_variant	28/28	ENST00000447944.7	NP_149100.2
PNPT1	XM_005264629.3	c.*71T>C		3_prime_UTR_variant	28/28		XP_005264686.1
PNPT1	XM_017005172.2	c.*71T>C		3_prime_UTR_variant	27/27		XP_016860661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPT1	ENST00000447944.7	c.*71T>C		3_prime_UTR_variant	28/28	1	NM_033109.5	ENSP00000400646	P1
PNPT1	ENST00000260604.8	c.*1965T>C		3_prime_UTR_variant, NMD_transcript_variant	27/27	5		ENSP00000260604
PNPT1	ENST00000415374.5	c.*71T>C		3_prime_UTR_variant, NMD_transcript_variant	28/29	5		ENSP00000393953

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3629 AN: 152114 Hom.: 149 Cov.: 33

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00253 AC: 2419 AN: 956484 Hom.: 91 Cov.: 12 AF XY: 0.00217 AC XY: 1046 AN XY: 481068

Gnomad4 AFR exome AF: 0.0843

Gnomad4 AMR exome AF: 0.00610

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000201

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000142

Gnomad4 OTH exome AF: 0.00613

GnomAD4 genome AF: 0.0239 AC: 3634 AN: 152232 Hom.: 149 Cov.: 33 AF XY: 0.0229 AC XY: 1708 AN XY: 74466

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0131 Hom.: 18

Bravo AF: 0.0274

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs72930820; hg19: chr2-55863301;