8-100705029-G-A

Position:

• chr8-100705029-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002568.4(PABPC1):​c.1715C>T​(p.Ala572Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PABPC1 NM_002568.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.15

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31731796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PABPC1	NM_002568.4	c.1715C>T	p.Ala572Val	missense_variant	13/15	ENST00000318607.10
PABPC1	XM_005250861.4	c.1715C>T	p.Ala572Val	missense_variant	13/15
PABPC1	XM_047421694.1	c.1715C>T	p.Ala572Val	missense_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC1	ENST00000318607.10	c.1715C>T	p.Ala572Val	missense_variant	13/15	1	NM_002568.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.1715C>T (p.A572V) alteration is located in exon 13 (coding exon 13) of the PABPC1 gene. This alteration results from a C to T substitution at nucleotide position 1715, causing the alanine (A) at amino acid position 572 to be replaced by a valine (V). 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	0.23
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T;T;T;T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D;D;T;D;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L;.;.;.;.;.
MutationTaster	Benign	0.51	N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N;N;N;N;N;.
REVEL	Benign	0.088
Sift	Benign	0.17	T;T;T;D;T;.
Sift4G	Benign	0.26	T;T;T;D;T;T
Polyphen		0.0050	B;.;B;.;.;.
Vest4		0.32
MutPred		0.44		Loss of disorder (P = 0.0601);.;.;.;.;.;
MVP		0.58
MPC		1.3
ClinPred		0.63	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.73

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: chr8-101717257;