Variant 2-60756491-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022894.4(PAPOLG):c.13T>C(p.Ser5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PAPOLG
NM_022894.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

Variant links:

Genes affected

PAPOLG (HGNC:14982): (poly(A) polymerase gamma) This gene encodes a member of the poly(A) polymerase family which catalyzes template-independent extension of the 3' end of a DNA/RNA strand. This enzyme shares 60% identity to the well characterized poly(A) polymerase II (PAPII) at the amino acid level. These two enzymes have similar organization of structural and functional domains. This enzyme is exclusively localized in the nucleus and exhibits both nonspecific and CPSF (cleavage and polyadenylation specificity factor)/AAUAAA-dependent polyadenylation activity. This gene is located on chromosome 2 in contrast to the PAPII gene, which is located on chromosome 14. [provided by RefSeq, Jul 2008]

PAPOLG links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17053685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPOLG	NM_022894.4 link	c.13T>C	p.Ser5Pro	missense_variant	Exon 1 of 22	ENST00000238714.8	NP_075045.2	Q9BWT3-1
PAPOLG	XM_005264500.5 link	c.13T>C	p.Ser5Pro	missense_variant	Exon 1 of 21		XP_005264557.1	Q9BWT3-2
PAPOLG	XM_005264501.3 link	c.-116+142T>C		intron_variant	Intron 1 of 21		XP_005264558.1
PAPOLG	XR_007080681.1 link	n.224T>C		non_coding_transcript_exon_variant	Exon 1 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PAPOLG	ENST00000238714.8 link	c.13T>C	p.Ser5Pro	missense_variant	Exon 1 of 22	1	NM_022894.4	ENSP00000238714.3	Q9BWT3-1
PAPOLG	ENST00000414060.5 link	n.-116+142T>C		intron_variant	Intron 1 of 20	1		ENSP00000405599.1	F8WAT4
PAPOLG	ENST00000496283.5 link	n.97+142T>C		intron_variant	Intron 1 of 18	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.13T>C (p.S5P) alteration is located in exon 1 (coding exon 1) of the PAPOLG gene. This alteration results from a T to C substitution at nucleotide position 13, causing the serine (S) at amino acid position 5 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.69

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.26

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.020

REVEL

Benign

0.28

Sift

Benign

0.080

Sift4G

Benign

0.089

Polyphen

0.021

Vest4

0.42

MutPred

0.19

Gain of loop (P = 0.0502);

MVP

0.83

MPC

0.89

ClinPred

0.50

GERP RS

3.8

Varity_R

0.23

gMVP

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over