NM_032632.5:c.1832C>G

Variant names:

• chr14-96556241-C-G
• rs144871315
• NM_032632.5:c.1832C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032632.5(PAPOLA):​c.1832C>G​(p.Thr611Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T611A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAPOLA NM_032632.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15
• Publications: 0 publications found

Genes affected

PAPOLA (HGNC:14981): (poly(A) polymerase alpha) The protein encoded by this gene belongs to the poly(A) polymerase family. It is required for the addition of adenosine residues for the creation of the 3'-poly(A) tail of mRNAs. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2902757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPOLA	NM_032632.5	c.1832C>G	p.Thr611Arg	missense_variant	Exon 19 of 22	ENST00000216277.13	NP_116021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPOLA	ENST00000216277.13	c.1832C>G	p.Thr611Arg	missense_variant	Exon 19 of 22	1	NM_032632.5	ENSP00000216277.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.56	T;T;.
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.0	M;.;.
PhyloP100		4.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.087
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.22	T;T;T
Polyphen		0.88	P;.;.
Vest4		0.53
MutPred		0.29		Gain of catalytic residue at P606 (P = 0);Gain of catalytic residue at P606 (P = 0);.;
MVP		0.41
MPC		0.36
ClinPred		0.66	D
GERP RS		6.0
Varity_R		0.13
gMVP		0.57
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs144871315; hg19: chr14-97022578;