Variant chr8-100713178-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002568.4(PABPC1):c.647C>G(p.Pro216Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,433,710 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PABPC1
NM_002568.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38

Variant links:

Genes affected

PABPC1 (HGNC:8554): (poly(A) binding protein cytoplasmic 1) This gene encodes a poly(A) binding protein. The protein shuttles between the nucleus and cytoplasm and binds to the 3' poly(A) tail of eukaryotic messenger RNAs via RNA-recognition motifs. The binding of this protein to poly(A) promotes ribosome recruitment and translation initiation; it is also required for poly(A) shortening which is the first step in mRNA decay. The gene is part of a small gene family including three protein-coding genes and several pseudogenes.[provided by RefSeq, Aug 2010]

PABPC1 links:

PABPC1 (HGNC:):

PABPC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PABPC1	NM_002568.4 linkuse as main transcript	c.647C>G	p.Pro216Arg	missense_variant	5/15	ENST00000318607.10	NP_002559.2	P11940-1A0A024R9C1
PABPC1	XM_005250861.4 linkuse as main transcript	c.647C>G	p.Pro216Arg	missense_variant	5/15		XP_005250918.1	P11940-1A0A024R9C1
PABPC1	XM_047421694.1 linkuse as main transcript	c.647C>G	p.Pro216Arg	missense_variant	5/14		XP_047277650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PABPC1	ENST00000318607.10 linkuse as main transcript	c.647C>G	p.Pro216Arg	missense_variant	5/15	1	NM_002568.4	ENSP00000313007.5		P11940-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000442

AC:

AN:

226236

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1433710

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000258

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:

0.0000169

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.647C>G (p.P216R) alteration is located in exon 5 (coding exon 5) of the PABPC1 gene. This alteration results from a C to G substitution at nucleotide position 647, causing the proline (P) at amino acid position 216 to be replaced by an arginine (R). 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

0.28

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.051

T;T;T;T

Eigen

Benign

-0.069

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.65

T;T;T;T

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.57

D;D;D;D

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.82

L;.;.;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.49

N;N;N;.

REVEL

Benign

0.27

Sift

Benign

0.17

T;T;T;.

Sift4G

Benign

0.37

T;T;T;T

Polyphen

0.0020

B;.;B;.

Vest4

0.68

MutPred

0.60

Gain of MoRF binding (P = 0.0039);.;.;.;

MVP

0.83

MPC

1.3

ClinPred

0.47

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over