2-55636268-G-C

Position:

• chr2-55636268-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033109.5(PNPT1):​c.2321C>G​(p.Pro774Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PNPT1 NM_033109.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03637275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPT1	NM_033109.5	c.2321C>G	p.Pro774Arg	missense_variant	28/28	ENST00000447944.7	NP_149100.2
PNPT1	XM_005264629.3	c.2081C>G	p.Pro694Arg	missense_variant	28/28		XP_005264686.1
PNPT1	XM_017005172.2	c.2081C>G	p.Pro694Arg	missense_variant	27/27		XP_016860661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPT1	ENST00000447944.7	c.2321C>G	p.Pro774Arg	missense_variant	28/28	1	NM_033109.5	ENSP00000400646	P1
PNPT1	ENST00000415374.5	c.2321C>G	p.Pro774Arg	missense_variant, NMD_transcript_variant	28/29	5		ENSP00000393953
PNPT1	ENST00000260604.8	c.*1863C>G		3_prime_UTR_variant, NMD_transcript_variant	27/27	5		ENSP00000260604

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460588 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726570

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.39	N
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.075
Sift	Benign	0.18	T
Sift4G	Benign	0.062	T
Polyphen		0.0	B
Vest4		0.054
MutPred		0.31		Gain of MoRF binding (P = 0.0019);
MVP		0.18
MPC		0.15
ClinPred		0.22	T
GERP RS		5.0
Varity_R		0.051
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-55863403;